Bacterial Bioprospecting for Obtaining Antibiotic Substances against Staphylococcus aureus and Pseudomonas aeruginosa: A Literature Review

Abstract

The decline in antibiotic development, alongside the increasing prevalence of multidrug-resistant bacteria, highlights the urgent need for new antimicrobial agents. Among the pathogens prioritized by the World Health Organization for antimicrobial research and development are Staphylococcus aureus and Pseudomonas aeruginosa, which are associated with severe infections and significant resistance mechanisms that compromise treatment efficacy. In this context, bioprospecting has emerged as a promising strategy for identifying new antimicrobial compounds from diverse biological sources. This integrative literature review synthesized current methodologies used for the isolation, cultivation, processing, extraction, and identification of antibiotic-producing bacteria active against S. aureus and P. aeruginosa, providing an overview of approaches applied to pathogens of critical clinical relevance. The review was conducted using the MEDLINE portal through the PubMed database, and included in vitro studies published in English between 2020 and 2025 that aligned with the proposed objective, resulting in 44 eligible articles. The findings demonstrated that marine environments, soil, food sources, and the human microbiota are the primary sources of bacteria with antimicrobial potential against these pathogens. Lactic acid bacteria were the most frequently identified group, although other bacterial genera were also reported, such as Bacillus. Cultivation conditions varied according to the bacterial species and study objectives. Antibiotic substances were predominantly obtained through solvent extraction and ammonium sulfate precipitation, while structural characterization relied mainly on chromatographic techniques, nuclear magnetic resonance spectroscopy, and mass spectrometry. Overall, this review consolidates current methodological strategies in antimicrobial bioprospecting and may support future studies focused on the discovery and development of new antibacterial compounds targeting WHO priority pathogens.

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Valente, G. , Martins, F. , Paula, G. and Lima, A. (2026) Bacterial Bioprospecting for Obtaining Antibiotic Substances against Staphylococcus aureus and Pseudomonas aeruginosa: A Literature Review. Open Journal of Medical Microbiology, 16, 166-197. doi: 10.4236/ojmm.2026.163009.

1. Introduction

The decline in antibiotic development [1] has occurred in parallel with the emergence of multidrug-resistant bacteria, that is, those that are resistant to more than three classes of antibiotics [2] [3]. Therefore, the search for new antimicrobial drugs is of great importance, given that some classic pathogens have a great capacity to acquire and disseminate resistance genes, making them global public health problems [4]-[7].

In 2017, the World Health Organization (WHO) published a list of pathogens for which the development of new antimicrobials is an urgent matter, with the aim of guiding research and development of these drugs. In this context, the ESKAPE group, an acronym for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp., was designated as a priority target [8] [9].

Staphylococcus aureus is a Gram-positive bacterium and one of the most widespread pathogenic species, capable of causing serious infections such as respiratory tract infections, surgical site infections, cardiovascular infections, nosocomial infections, and skin infections, since this pathogen is commonly found on the skin of healthy people, being able to invade mucous membranes or penetrate the skin barrier in cases of wounds [10]-[13]. S. aureus bacteremia has an incidence rate between 20 and 50 cases per 100,000 people per year, with a mortality rate of 10 to 30% [13] [14]. Methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to several β-lactams commonly used in clinical practice, such as methicillin itself, penicillin, amoxicillin, and oxacillin [15]. Methicillin resistance rates in clinical isolates can reach more than 50% of cases in the United States and China [16], 25.9% for healthcare-associated bloodstream infections in Brazil [17] and are on the rise in developing countries in Africa [13] [18].

Pseudomonas aeruginosa is a motile, non-fermenting Gram-negative bacterium commonly found in aquatic environments such as lakes, rivers, and swimming pools, as well as on plants, fruits, soil, animals, food, and in humans [19]-[22]. It is capable of causing opportunistic infections, especially in immunocompromised patients, post-surgical patients, or those in intensive care units, as well as patients with cystic fibrosis, burns, or diabetes mellitus [22]-[27]. It is also the most frequent colonizer of medical devices and one of the pathogens most associated with nosocomial infections [20] [28]. This bacterium commonly exhibits multidrug resistance characteristics, both naturally occurring and acquired, which makes the treatment of infections caused by this pathogen a challenge [20] [29].

The increasing prevalence of multidrug-resistant pathogens underscores the urgency of exploring safer alternative treatments [30] [31]. Conventional approaches, such as the chemical modification of existing antibiotics and synthetic drug development, have faced limitations due to high costs, long development timelines, and the rapid emergence of bacterial resistance. In this scenario, a possible alternative would be bioprospecting, which is characterized as the exploration of biodiversity in search of new biological resources with economic and social value. This process is carried out by various industries, notably the pharmaceutical industry, but also in sectors such as agriculture, manufacturing, engineering, construction, and others [32] [33].

This study aimed to analyze the methodological approaches used for the isolation, cultivation, and processing of antibiotic producing bacteria active against Staphylococcus aureus and Pseudomonas aeruginosa, focusing on their sources, diversity, growth conditions, and the main methods employed for the extraction and identification of bioactive molecules.

2. Materials and Methods

2.1. Type of Study and Field of Research

This is an integrative literature review, conducted using the MEDLINE portal and the PubMed database. The PICo strategy (acronym for Population/Problem, Interest, and Context) was used to formulate the research question, enabling the identification of descriptors that aid in locating relevant primary studies in the databases [34]. Table 1 illustrates the formulation of the research question using this strategy.

Table 1. Formulating the research question—PICo strategy.

PICo strategy

P

Bacteria that produce antibiotic substances against Staphylococcus aureus and Pseudomonas aeruginosa.

I

Strategies for obtaining, cultivating and processing, including growing conditions and methodologies for extraction and identification.

Co

Characterization of the sources of isolation, diversity, conditions and methods used.

Thus, the delimited research question is: “What are the main strategies for obtaining, cultivating, and processing bacteria that produce antibiotic substances against Staphylococcus aureus and Pseudomonas aeruginosa described in the literature, considering their sources of isolation, taxonomic diversity, growth conditions, and methods of extraction and identification of bioactive molecules?” The keywords were selected from the Health Sciences Descriptors of the BVS and MeSH Database, using Boolean operators “AND” and “OR” to combine the terms: Anti-Bacterial Agents; Peptides; Bacteriocins; Lipopeptides; Enzymes; Biofilms; Bioprospecting; Metabolome; Microbiota; Supernatant; Wound healing; Wound infection; Cell-free supernatant; Cell-free extract; Chromatography, High Pressure Liquid; Liquid Chromatography-Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular; Proton Magnetic Resonance Spectroscopy; Magnetic Resonance Spectroscopy; Staphylococcus aureus; Pseudomonas aeruginosa.

2.2. Sampling

The sampling method used was sequential, which consists of recruiting all accessible productions that meet the eligibility criteria over a specific time interval [35], which was conveniently limited to the last five years.

The inclusion criteria used are: in vitro studies, adherence to the objective and the proposed theme, articles published in full, in English, with a publication time frame from 2020 to 2025.

Exclusion criteria: Duplicate articles, literature reviews, texts unavailable in full format, isolated case reports, opinion articles, and those that did not address the defined topic.

Data was collected from the PubMed database, maintained by the National Institutes of Health (NIH). This database was selected because of its broad coverage of biomedical and microbiological literature relevant to the scope of this review. The respective descriptors and Boolean operators were used: [(((Anti-Bacterial Agents) OR (Peptides) OR (Bacteriocins) OR (Lipopeptides) OR (Enzymes) OR (Biofilms)) AND ((Bioprospecting) OR (Metabolome) OR (Microbiota) OR (Supernatant) OR (Wound Healing) OR (Wound Infection) OR (cell-free supernatant) OR (cell-free extract) OR (Chromatography, High Pressure Liquid) OR (Liquid Chromatography-Mass Spectrometry) OR (Nuclear Magnetic Resonance, Biomolecular) OR (Proton Magnetic Resonance Spectroscopy) OR (Magnetic Resonance Spectroscopy)) AND ((Staphylococcus aureus) OR (Pseudomonas aeruginosa)) NOT (plants) NOT (herbal) NOT (Oils, Volatile) NOT (oils) NOT (phytochemicals) NOT (intestine) NOT (in vivo) NOT (mice) NOT (Capsules) NOT (gut) NOT (dental plaque) NOT (probiotics) NOT (seaweed) NOT (fungi) NOT (virus) NOT (silver) NOT (zinc) NOT (gold) NOT (metals) NOT (Hydrogels) NOT (Review [Publication Type]))]. Restrictive NOT filters related to probiotics and gut-associated terms were applied to narrow the scope of the review and avoid the overrepresentation of studies involving probiotic microorganisms and intestinal microbiota, which are already extensively described in the literature. The objective of these exclusions was to focus the search on less explored bacterial sources with potential for antibacterial bioprospecting.

After searching the aforementioned database, the articles were refined beforehand by reading the abstract and selected after a complete reading of the text, to ensure they met the inclusion criteria. A flowchart of the search was created, containing the databases and the number of publications located. Search filters were also applied, based on the inclusion and exclusion criteria, to select potential bibliography for this study using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), as shown in the flowchart (Figure 1).

Figure 1. Article selection flowchart.

After applying the descriptors and Boolean operators in PubMed/MEDLINE, a total of 3882 articles were identified. Subsequently, filters for articles published in English and within the last five years were applied, resulting in 3689 and 847 articles, respectively. No duplicate articles were identified due to the use of a single database. The titles and abstracts of the 847 articles were screened, and 44 studies were considered eligible and included in the review after full-text assessment. The main reasons for exclusion during the screening process were studies conducted exclusively or predominantly in vivo (n = 79), articles not adherent to the proposed objective and theme of the review (n = 521), literature reviews (n = 194), case reports (n = 7), and opinion articles (n = 2). Study selection and data extraction were performed by a single reviewer according to the established eligibility criteria. Due to the integrative nature of this review and the methodological heterogeneity among the included in vitro studies, no formal methodological quality appraisal tool was applied. The studies were evaluated based on their relevance to the proposed objective and the established eligibility criteria.

The data extracted from the selected studies were organized into a spreadsheet, arranged in manually assigned sequential numbers, and which includes information such as number, authors, year, title, genera or species of antibiotic-producing bacteria and their culture parameters, source of isolation of the producing bacteria, target species of the study, molecule extraction method used, identification method used, and nature or identification of the bioactive molecule.

The methods used to identify the biomolecules present in the supernatants were classified as follows:

  • Separation techniques only: Thin Layer Chromatography (TLC), Cation Exchange Chromatography (CIEX), C18 chromatographic column, High-performance liquid chromatography (HPLC), Ion Exchange Chromatography (IEX), Reversed Phase High-performance liquid chromatography (RP-HPLC), Reversed-phase Chromatography (RPC) and Size Exclusion Chromatography (SEC);

  • Spectroscopic techniques: Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR);

  • Spectrometric techniques: Mass Spectrometry (MS), Electrospray Ionization Mass Spectrometry (ESI-MS) and Electrospray Ionization coupled to Mass Spectrometry (ESI-MS/MS);

  • Electrophoretic techniques: Polyacrylamide Gel Electrophoresis (PAGE) and Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE);

  • Hybrid techniques: Gas Chromatography coupled to Mass Spectrometry (GC-MS), High Performance Liquid Chromatography coupled to Mass Spectrometry (HPLC-MS), High Performance Liquid Chromatography coupled to UV-Visible Detector (HPLC-UV), Liquid Chromatography coupled to High-Resolution Mass Spectrometry (LC-HRMS), Liquid chromatography-mass spectrometry (LC-MS), Liquid chromatography-mass spectrometry coupled with mass spectrometry (LC-MS/MS), High-Resolution Mass Spectrometry coupled with ultraviolet detector and Liquid Chromatography (LC-UV-HRMS), Ultra-High Performance Liquid Chromatography coupled to a Diode Array Detector (UHPLC-DAD), Ultra-High Performance Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS), Ultra-High Performance Liquid Chromatography coupled to a Diode Detector and Mass Spectrometer (UPLC-DAD-MS), Ultra-High Performance Liquid Chromatography with High-Resolution Mass Spectrometry and Tandem Mass Spectrometry (UPLC-HR-MS/MS) and Ultra Performance Liquid Chromatography coupled to UV-Visible Detector (UPLC-UV).

The publications were analyzed separately, and the studies selected for this review were categorized using codes from 1 to 44. The results are presented in tables, primarily aiming to demonstrate the aspects identified as most relevant, according to the objectives of this study.

3. Results and Discussion

3.1. Overview of Antibiotic-Producing Bacteria and Study Characteristics

After reviewing the selected bibliographic material, information was extracted that answered the guiding research question: “What are the main strategies for obtaining, cultivating, and processing bacteria that produce antibiotic substances against Staphylococcus aureus and Pseudomonas aeruginosa described in the literature, considering their sources of isolation, taxonomic diversity, growth conditions, and methodologies for extracting and identifying bioactive molecules?” The overview of the articles found, in relation to the species that produce antibiotic substances and their sources of isolation, and target species, is presented in Table S1.

3.1.1. Genera of Antibiotic-Producing Bacteria and Target Pathogens

Among the target species evaluated in the included studies (Table S2), Staphylococcus aureus was the most frequently investigated, appearing in 32 out of 44 studies (72.7%). Some studies simultaneously analyzed Staphylococcus aureus and Pseudomonas aeruginosa, with 9 out of 44 studies (20.5%), while only a small number of articles focused exclusively on Pseudomonas aeruginosa, representing 3 out of 44 studies (6.8%). This overview shows that, although both species are relevant pathogens, there is a predominance of studies focused on the potential use of bacterial supernatants in prospecting for molecules with activity against S. aureus, while P. aeruginosa remains relatively unexplored, representing a gap and, at the same time, a promising opportunity for future investigations.

Regarding the genera of bacteria that produce bioactive substances, there is a predominance of the genus Bacillus, one of the bacterial genera most associated with its ability to produce enzymes and proteins [36], with 13 species belonging to this genus being used in the studies (Table S3). Furthermore, there is a predominance of lactic acid bacteria genera, which includes genera such as Brevibacillus, Enterococcus, Lacticaseibacillus, Lactiplantibacillus, Lactobacillus, Lactococcus, Ligilactobacillus, Loigolactobacillus, Pediococcus, and Vagococcus.

Among the species of the genus Bacillus, the one that stood out the most was Bacillus subtilis, present in 3 studies. B. subtilis is a Gram-positive bacterium that forms heat-resistant spores as part of its life cycle and is reported as a fast-growing bacterium. Its genetic material can also be manipulated due to its ability to acquire external DNA and integrate it into its genome, making this species one of the most studied bacteria for this type of function, along with Escherichia coli [37].

Because it is a non-pathogenic, versatile, and easy-to-cultivate bacterium, B. subtilis can be used for various purposes, such as the production of traditional foods in Asia and the production of vitamins, amino acids, and enzymes [37]. Due to the many applications of B. subtilis being associated with its ability to produce and secrete proteins, research has focused on its secretome, which includes both its protein secretion machinery and the proteins themselves [36].

These findings demonstrate the importance of bioprospecting as a methodology for obtaining bioactive molecules, given the variety of species found that can be used for this purpose. Li and collaborators [38] used species from the genera Lactiplantibacillus, Lactobacillus, and Ligilactobacillus, belonging to the lactic acid bacteria group, from different foods, obtaining bioactive molecules against P. aeruginosa. On the other hand, studies have used species that are not part of the lactic acid bacteria group, such as Staphylococcus pseudointermedius, isolated from the raccoon dog, which has shown the ability to produce molecules against S. aureus.

3.1.2. Sources of Isolation

Of all the reported sources of bacterial isolation, the marine environment was the most frequently cited, appearing in 13 studies (Table S4). This environment, especially bacteria isolated from marine sponges, has been shown in recent research to be a rich source of substances with diverse biological actions, particularly in relation to antibiotic or antibiofilm molecules [39], but also for applications in the energy, food, nutraceutical and biorefinery industries [3] [40] [41].

Food and soil are also explored sources, with 8 studies each obtaining species from these locations. Food production, for example, is closely linked to the relationship between microorganisms and plants, given that microorganisms present in the soil are able to participate in nutrient cycling and waste processing through the enzymes they produce, and such enzymes can be the target of bioprospecting processes [42]. Garcia-López and collaborators [43] used strains of Lactiplantibacillus paraplantarum and Pediococcus acidilactici isolated from sausages, finding activity against Listeria monocytogenes, Escherichia coli, Clostridium perfringens, and Staphylococcus aureus.

Among the sources investigated in the analyzed studies, the human microbiota remains comparatively underexplored as a source for antimicrobial-producing microorganisms, despite its recognized microbial diversity and biotechnological potential. Notably, only one study included in this review reported the use of intact human skin as a source for bioprospecting. The skin microbiome represents a highly diverse and dynamic ecological niche, shaped by continuous interactions between microorganisms and the host across one of the largest and most exposed surfaces of the human body. This unique ecological context suggests substantial, yet still largely untapped, potential for the discovery of new antibiotic substances. Therefore, expanding bioprospecting efforts toward the human microbiota may represent a promising direction for future research aimed at identifying new antimicrobial-producing microorganisms [44].

The resident skin microbiota is capable of producing antimicrobial peptides that, in the normal functioning of the human body, have the function and capacity to combat the establishment of external species at that site. Among these antimicrobial peptides, bacteriocins demonstrate this ability to inhibit pathogenic microorganisms in in vitro and in vivo studies [45]. Due to the need to discover new compounds with antibacterial activity to control the spread of antibiotic-resistant microorganisms, interest in the protective role played by the skin microbiota has increased. In the study by Pedretti and collaborators [44], a strain of Bacillus siamensis was isolated from intact skin and showed the ability to produce molecules with antimicrobial activity against several pathogenic species, such as Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, and Candida spp.

3.2. Methods for Bacterial Culture, Extraction and Identification of Bioactive Molecules

Table S5 summarizes the approaches used across studies for the discovery and characterization of antibiotic molecules, including extraction strategies, cultivation conditions, and the general types of analytical methods applied for compound identification. Collectively, this synthesis highlights the methodological diversity employed to obtain and characterize antibiotic substances with activity against antibiotic-resistant bacteria.

3.2.1. Culture Media

The main culture media used were Man, Rogosa and Sharpe (MRS) broth, used in 11 studies, and Luria-Bertani (LB) broth, used in 9 studies (Table S6). MRS broth, considered a rich culture medium, is the standard choice for the isolation of lactic acid bacteria. It uses glucose as a carbon source and various nitrogen sources in its composition, including yeast extract, meat extract, and peptone, and is supplemented with minerals that provide micronutrients [46] [47]. LB broth is a complex culture medium containing tryptone, yeast extract, and NaCl [48]. It is noted as one of the main culture media for bacteria, being a good source of energy for the growth of Lactobacillus and other lactic acid bacteria [49].

3.2.2. Incubation Temperature

The most frequent incubation temperatures were 37˚C and 30˚C, with 15 and 12 studies, respectively (Table S7). Each microorganism is adapted to specific temperature conditions for its cultivation, as evidenced by the work of Lei and collaborators [50], in which the species Lactobacillus plantarum isolated from human feces was cultivated at 37˚C, the temperature corresponding to its habitat at the time of collection and isolation. In contrast, the study by Shirazi and collaborators [51], which isolated the species Laceyella sacchari, Thermoactinomyces sp., and Laceyella sp. from the surroundings of volcanoes and other locations, cultivated these species at 50˚C, given that they are thermophilic microorganisms.

3.2.3. Incubation Times

The most frequently used incubation times were 24 and 48 hours, with 14 and 9 studies each, respectively (Table S8). In the work of Levenfors and collaborators [52], the incubation time varied between 4 and 7 days, in an attempt to evaluate the conditions under which the production of bioactive substances was optimized. This practice, along with variations in other cultivation parameters, can help determine the best yields for the production of substances of interest.

3.2.4. Shaking during Bacterial Growth

Regarding the use of shaking during the incubation of the culture medium containing the inoculum, 26 studies used this technique, while 15 did not (Table S9). During their growth, bacterial cultures in broth that are under agitation tend to have a higher growth rate, which can be attributed to the aeration of the medium due to the agitation process [53]. Therefore, this practice should be considered for experiments involving bioprospecting, when applicable, but taking into account the most suitable conditions for obtaining the bioactive substance.

3.2.5. Oxygen Availability

The most frequently observed oxygen availability in the studies was aerobic, with 34 studies using this incubation condition and 7 studies using anaerobic conditions (Table S10). The species cultivated in the absence of oxygen were Bacillus spp., Bacillus subtilis, Lacticaseibacillus rhamnosus, and Lactobacillus plantarum. These species are facultative anaerobes and can be cultivated under such conditions, especially if the biotechnological direction of their production of bioactive substances is promoted.

3.2.6. Extraction Methods

Among the methodologies used for the extraction of antibiotic molecules from bacterial culture supernatants, the organic solvent extraction method is the most widely used, being cited in 19 studies (Table S11).

The selection of molecules by different polarities allows the separation of the various components originating from bacterial metabolism [54], enabling phenotypic tests with smaller sets of molecules or even the isolated molecule. This approach is also important for the subsequent identification of molecules, since it makes it possible to know with greater certainty the bioactive molecule among several molecules produced by that species [55].

Another methodology used is ammonium sulfate precipitation, aiming at the separation of proteins present in the cell-free supernatant (CFS). This method was used in 13 studies and is based on the salting-out process, associated with the decrease in protein solubility when the salt concentration in the solution increases, allowing an increase in extraction yield and optimizing the protein purification process [56].

3.2.7. Identification Methods

After extracting the molecules of interest from their original CFS, another important step is the structural identification of that compound. The main methods found were Nuclear Magnetic Resonance (NMR), used in 10 studies, in addition to several methodologies based on chromatographic methods followed by mass spectrometry (Table S12).

In the studies included in this review, nuclear magnetic resonance (NMR) spectroscopy was primarily used for the structural elucidation of purified antibiotic substances obtained after extraction and preliminary fractionation steps. By providing one-dimensional spectra based on hydrogen spin analysis, NMR enabled detailed structural characterization, supporting compound identification with high reliability. In addition to its analytical robustness, NMR was frequently valued for being non-destructive, allowing sample recovery after analysis [57].

Mass spectrometry (MS) was widely applied for the detection and preliminary identification of bioactive molecules in complex biological extracts. In most studies, MS was coupled with separation techniques such as high-performance liquid chromatography (HPLC) or liquid chromatography (LC) to reduce sample complexity prior to ionization, commonly through electrospray ionization (ESI). This combined approach improved the detection of antimicrobial metabolites produced by the studied microorganisms [58]-[62].

Chromatographic techniques, particularly LC and GC, were consistently used as essential preparatory and separation steps before MS or, in some cases, NMR analysis. These methods enabled the fractionation of crude extracts and facilitated the isolation of antibiotic substances. In quantitative applications, LC-MS workflows frequently relied on targeted analyses using standards, although a recurring limitation across studies was the scarcity of appropriate reference compounds for absolute quantification. To address this, some studies employed isotopically labelled standards or metabolic labelling strategies to improve quantification accuracy in complex mixtures [63] [64].

4. Conclusions

This integrative review provides a consolidated overview of methodological strategies used for the isolation, cultivation, extraction, and identification of antibiotic-producing bacteria active against Staphylococcus aureus and Pseudomonas aeruginosa. Rather than focusing on isolated experimental outcomes, the synthesis highlights patterns in antimicrobial bioprospecting, including the convergence of a limited number of environmental sources, the recurrent use of specific cultivation media, and the predominance of established analytical workflows for compound characterization.

A key contribution of this review is the identification of research biases and knowledge gaps in the current literature. Although marine environments, soil, and food are the most frequently explored sources, this prevalence reflects historical research trends rather than confirmed superiority in antimicrobial yield. Notably, the human microbiota remains significantly underrepresented, despite its ecological diversity and strong potential as a source of new microorganisms for bioprospecting. In addition, research efforts are more concentrated on S. aureus, while P. aeruginosa, a critical WHO priority pathogen, receives less attention in terms of bioprospecting strategies and microbial sources.

Overall, the reviewed studies demonstrate shared methodological frameworks in cultivation and compound recovery, particularly the use of nutrient-rich media, specific incubation periods, and conventional extraction approaches, which may limit the discovery of less readily cultivable or slow-growing producers. Similarly, reliance on established analytical pipelines such as chromatography, NMR, and mass spectrometry reinforces the identification of known compound classes, potentially limiting chemical novelty.

These findings emphasize the need to diversify both ecological sources and methodological approaches in future studies, particularly by expanding investigations into underexplored microbiomes such as the human-associated microbiota and by strengthening targeted efforts against P. aeruginosa. In this sense, the present review not only compiles existing methodologies but also highlights critical gaps that can guide more innovative and discovery-oriented bioprospecting strategies. By integrating these perspectives, this synthesis contributes to the advance of antimicrobial research aimed at addressing the global challenge of multidrug resistance.

A limitation of this review is the exclusive use of PubMed/MEDLINE, which may have resulted in the exclusion of relevant studies indexed in other databases, such as Scopus, Web of Science, and Embase. Additionally, study selection and data extraction were conducted by a single reviewer, which may increase the risk of selection bias or data extraction errors. The absence of a formal methodological quality assessment may limit the comparison of the robustness of the included studies.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001. It was also supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) (Grant numbers E-26/211.569/2021; E-26/210.915/2021; E-26/211.045/2024).

Author Contributions

Gabriel Luis Cavalcanti Valente: Conceptualization; Methodology; Investigation; Formal analysis; Data curation; Visualization; Writing—original draft; Writing—review & editing.

Francislene Juliana Martins: Methodology; Investigation; Data curation; Writing—review & editing.

Geraldo Renato de Paula: Formal analysis; Validation; Visualization; Writing—review & editing.

Adriene Ribeiro Lima: Conceptualization; Supervision; Resources; Project administration; Funding acquisition; Writing—review & editing.

Supplement

Table S1. Identification of the articles evaluated, types of bacteria producing antibiotic substances, sources of isolation and target species of the studies.

N

First author

Year

Article’s title

Biomolecule-producing species

Source of isolation

Target species of the study

1

Pedretti [44]

2024

Cell-Free Supernatant from a Strain of Bacillus siamensis Isolated from the Skin Showed a Broad Spectrum of Antimicrobial Activity.

Bacillus siamensis

Intact skin

Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, Candida spp.

2

Ogunsile [15]

2023

Anti-Methicillin-Resistant Staphylococcus aureus and Antibiofilm Activity of New Peptides Produced by a Brevibacillus Strain.

Brevibacillus sp.

Soil

Staphylococcus aureus

3

Songnaka [65]

2022

Purification and Characterization of Novel Anti-MRSA Peptides Produced by Brevibacillus sp. SPR-20.

Brevibacillus sp.

Soil

Staphylococcus aureus

4

Kaweewan [66]

2020

Isolation and Structure Determination of a New Antibacterial Peptide Pentaminomycin C from Streptomyces cacaoi subsp. cacaoi.

Streptomyces cacaoi subsp. cacaoi

Food (cocoa)

Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus

5

Lin [67]

2021

Multi-Omics Analysis Reveals Anti-Staphylococcus aureus Activity of Actinomycin D Originating from Streptomyces parvulus.

Streptomyces parvulus

Marine environment (coral)

Staphylococcus aureus

6

Kokkini [68]

2022

Exploring Micromonospora as Phocoenamicins Producers.

Micromonospora sp.

Marine environment

Staphylococcus aureus, Mycobacterium tuberculosis, Mycobacterium bovis

7

Zhang [69]

2023

Two Antimicrobial Peptides Derived from Bacillus and Their Properties.

Bacillus spp.

Food

Staphylococcus aureus, Bacillus cereus, Salmonella enterica

8

Suaifan [70]

2023

Antibiotic—Lysobacter enzymogenes Proteases Combination as a Novel Virulence Attenuating Therapy.

Lysobacter enzymogenes

Data not provided

Staphylococcus aureus, Escherichia coli

9

Levenfors [52]

2020

Antibacterial Pyrrolidinyl and Piperidinyl Substituted 2,4-diacetylphloroglucinols from Pseudomonas protegens UP46.

Pseudomonas protegens

Soil

Staphylococcus aureus, Bacillus cereus

10

Santos [7]

2022

Antimicrobial Activity of Supernatants Produced by Bacteria Isolated from Brazilian Stingless Bee’s Larval Food.

Staphylococcus epidermidis, Providencia rettgeri, Enterococcus faecalis, Vagococcus fluvialis, Serratia marcescens

Animal (stingless bees)

Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus

11

Romero-González [71]

2023

Genomic and Phenotypic Characterization of Pseudomonas sp. GOM7, a Novel Marine Bacterial Species with Antimicrobial Activity against Multidrug-Resistant Staphylococcus aureus.

Pseudomonas sp.

Marine environment

Staphylococcus aureus

12

Gharaei [72]

2022

Isolation, Optimization, and Structural Characterization of Glycolipid Biosurfactant Produced by Marine Isolate Shewanella algae B12 and Evaluation of Its Antimicrobial and Anti-Biofilm Activity.

Shewanella algae

Marine environment

Bacillus cereus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Acinetobacter sp.

13

Tariq [73]

2023

Agonistic Antibacterial Potential of Loigolactobacillus coryniformis BCH-4 Metabolites against Selected Human Pathogenic Bacteria: An in Vitro and in Silico Approach.

Loigolactobacillus coryniformis

Data not provided

Escherichia coli, Bacillus cereus, Staphylococcus aureus

14

Ye [74]

2020

8-Deoxy-Rifamycin Derivatives from Amycolatopsis mediterranei S699 ΔrifT Strain.

Amycolatopsis mediterranei

Data not provided

Staphylococcus aureus

15

Ramalingam [75]

2022

Structural Characterization, Antimicrobial, Antibiofilm, Antioxidant, Anticancer and Acute Toxicity Properties of N-(2-hydroxyphenyl)-2-phenazina mine From Nocardiopsis exhalans (KP149558).

Nocardiopsis exhalans

Marine environment (Coral)

Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus

16

Wei [76]

2022

Isolation and Characterization of Bacteriocin-Producing Lacticaseibacillus rhamnosus XN2 from Yak Yoghurt and Its Bacteriocin.

Lacticaseibacillus rhamnosus

Food (Yak Yoghurt)

Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Brochothrix thermosphacta, Clostridium butyricum, Staphylococcus aureus, Listeria innocua, Listeria monocytogenes, Escherichia coli

17

Zhu [77]

2021

Purification, Characterization, and Mode of Action of Paracin 54, a Novel Bacteriocin against Staphylococci.

Lactobacillus paracasei

Feces

Staphylococcus aureus

18

Mlambo [78]

2022

Bioactive Metabolites of Lactiplantibacillus plantarum K014 against Methicillin-Resistant Staphylococcus aureus ATCC43300 and in Vitro Evaluation of Its Antibacterial, Antioxidant and Anti-inflammatory Activities.

Lactiplantibacillus plantarum

Food (dairy products)

Staphylococcus aureus

19

Trabelsi [79]

2022

Study of the Antimicrobial Potential of Actinomycetes Isolated from Organic and Inorganic Waste.

Actinomyces sp.

Compost pile

Candida albicans, Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli

20

Yang [80]

2020

Antibiotic Angucycline Derivatives from the Deepsea-Derived Streptomyces lusitanus.

Streptomyces lusitanus

Marine environment

Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus

21

Sarjoughian [81]

2020

Bioactivity of Bac70 Produced by Bacillus atrophaeus Strain DDBCC70.

Bacillus atrophaeus

Soil (desert)

Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus

22

Guo [82]

2020

Mining, Heterologous Expression, Purification and Characterization of 14 Novel Bacteriocins from Lactobacillus rhamnosus LS-8.

Lactobacillus rhamnosus

Food (chinese fermented pickles)

Escherichia coli, Staphylococcus aureus

23

Nunes [39]

2021

Antimicrobial and Antibiofilm Activities of Marinesponge-Associated Bacteria against Multidrug-Resistant Staphylococcus spp. Isolated from Canine Skin.

Bacillus algicola, Bacillus circulans, Bacillus pumilus, Bacillus sp., Kocuria sp., Pseudomonas denitrificans, Pseudomonas fluorescens, Pseudomonas putida, Pseudovibrio ascidiaceicola, Pseudovibrio denitrificans, Pseudovibrio sp.

Marine environment (sponge)

Staphylococcus pseudintermedius, S. schleiferi, S. aureus, S. sciuri, S. cohnii, S. simulans, S. auricularis, S. capitis, S. epidermidis, Staphylococcussp.

24

Yoshimura [83]

2024

Five New Analogs of Streptogramin Antibiotic Viridogrisein Isolated from Streptomyces niveoruber.

Streptomyces niveoruber

Data not provided

Staphylococcus aureus

25

Chakraborty [84]

2022

Bacillibactin Class of Siderophore Antibiotics from a Marine Symbiotic Bacillus as Promising Antibacterial Agents.

Bacillus amyloliquefaciens

Marine environment (algae)

Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae

26

Cavanaugh [85]

2021

Exiguobacterium sp. Is Endowed with Antibiotic Properties against Gram Positive and Negative Bacteria.

Exiguobacterium sp.

Marine environment (pond)

Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa

27

Mousavi [86]

2023

Antibacterial Properties of Bacteriocin Purified from Serratia marcescens and Computerized Assessment of its Interaction with Antigen 43 in Escherichia coli

Serratia marcescens

Shrimp farming tank

Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Vibrio fischeri, Vibrio harveyi

28

Silva [87]

2022

Insights into the Antimicrobial Activities and Metabolomes of Aquimarina (Flavobacteriaceae, Bacteroidetes) Species from the Rare Marine Biosphere.

Sarcotragus spinosulus, Ircinia variabilis, Eunicella labiata, Aquimarina muelleri, Aquimarina spongiae, Aquimarina latercula

Marine environment

Staphylococcus aureus

29

Naveed [88]

2023

Purification, Characterization and Bactericidal Action of Lysozyme, Isolated from Bacillus subtillis BSN314: A Disintegrating Effect of Lysozyme on Gram-Positive and Gram-Negative Bacteria.

Bacillus subtilis

Data not provided

Bacillus subtilis, Micrococcus luteus, Bacillus cereus, Salmonella typhimurium, Pseudomonas aeruginosa

30

Wang [89]

2020

Hetiamacin E and F, New Amicoumacin Antibiotics from Bacillus subtilis PJS Using MS/MS-Based Molecular Networking.

Bacillus subtilis

Soil (desert)

Staphylococcus epidermidis, Staphylococcus aureus

31

Mao [90]

2023

Impact of Cell-Free Supernatant of Lactic Acid Bacteria on Staphylococcus aureus Biofilm and Its Metabolites.

Bactérias ácido-láticas

Cow milk

Staphylococcus aureus

32

Hioki [91]

2021

Heterologous Production of Active form of Beta-Lytic Protease by Bacillus subtilis and Improvement of Staphylolytic Activity by Protein Engineering.

Bacillus subtilis

Data not provided

Staphylococcus aureus

33

Zammuto [92]

2023

Lichenysin-Like Polypeptide Production by Bacillus licheniformis B3-15 and Its Antiadhesive and Antibiofilm Properties.

Bacillus licheniformis

Marine environment (hot springs)

Staphylococcus aureus, Pseudomonas aeruginosa

34

Gu [93]

2022

Isolation, Identification and Characterization of Two Kinds of Deep-Sea Bacterial Lipopeptides Against Foodborne Pathogens.

Bacillus sp.

Marine environment

Staphylococcus aureus, Pseudomonas aeruginosa

35

Dai [94]

2021

A Novel Bacteriocin from Lactobacillus pentosus ZFM94 and Its Antibacterial Mode of Action.

Lactobacillus pentosus

Feces

Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus

36

Yi [31]

2024

Human Milk-Derived Enterococcus faecalis HM20: A Potential Alternative Agent of Antimicrobial Effect against Methicillin-Resistant Staphylococcus aureus (MRSA).

Enterococcus faecalis

Human milk

Staphylococcus aureus

37

Madoromae [95]

2025

Investigating the Production and Synergistic Antibacterial Activity of Bacteriocin-Like Substance from Brevibacillus laterosporus SA-14 (TISTR 2453) for Enhanced Wound Healing.

Brevibacillus laterosporus

Air

Staphylococcus aureus

38

Baranova [96]

2024

Bacteriocin from the Raccoon Dog Oral Microbiota Inhibits the Growth of Pathogenic Methicillin-Resistant Staphylococcus aureus.

Staphylococcus pseudintermedius

Animal (racoon dog)

Staphylococcus aureus

39

Li [38]

2023

Screening and Metabolomic Analysis of Lactic Acid Bacteria-Antagonizing Pseudomonas aeruginosa.

Lactiplantibacillus plantarum, Lactobacillus acidophilus, Lactobacillus gasseri, Ligilactobacillus salivarius

Food (Fermented milk, pickles, Xizang’s kefir, fermented rice)

Pseudomonas aeruginosa

40

Kaya [97]

2020

Characterization of Pediococcus acidilactici PFC69 and Lactococcus lactis PFC77 Bacteriocins and Their Antimicrobial Activities in Tarhana Fermentation.

Pediococcus acidilactici, Lactococcus lactis

Food (Tarhana)

Bacillus cereus, Staphylococcus aureus

41

García-López [43]

2023

Lactiplantibacillus paraplantarum BPF2 and Pediococcus acidilactici ST6, Two Bacteriocinogenic Isolated Strains from Andalusian Spontaneous Fermented Sausages.

Lactiplantibacillus paraplantarum, Pediococcus acidilactici

Food (fermented sausages)

Listeria monocytogenes, Escherichia coli, Clostridium perfringens, Staphylococcus aureus

42

Bano [98]

2022

Bioprospecting of the Novel Isolate Microbacterium proteolyticum LA2(R) from the Rhizosphere of Rauwolfia Serpentina.

Microbacterium proteolyticum

Plants and soil

Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Salmonella abony

43

Lei [50]

2020

Partial Purification and Characterization of Abroad-Spectrum Bacteriocin Produced by a Lactobacillus plantarum Zrx03 Isolated from Infant’s Feces.

Lactobacillus plantarum

Feces

Staphylococcus aureus, Bacillus subtilis, Bacillus anthracis, Escherichia coli, Salmonella sp.

44

Shirazi [51]

2023

Isolation and Screening of Thermoactinomycetaceae Family Members as an Extremophilic Poor Investigated and Promising Natural Source of Antimicrobial Substances.

Laceyella sacchari, Thermoactinomyces sp., Laceyella sp.

Soil

Staphylococcus aureus

Table S2. Target species of the studies.

Target species of the studies

Number of appearances

Percentage of total

Staphylococcus aureus

32

72.7%

Pseudomonas aeruginosa

3

6.8%

Both species

9

20.5%

Table S3. Biomolecule-producing bacterial genera.

Biomolecule-producing bacterial genera

Number of appearances

Percentage of total

Aquimarina

3

4.3%

Bacillus

13

18.6%

Lactobacillus

7

10.0%

Streptomyces

4

5.7%

Actinomyces

1

1.4%

Amycolatopsis

1

1.4%

Brevibacillus

3

4.3%

Enterococcus

2

2.9%

Eunicella

1

1.4%

Exiguobacterium

1

1.4%

Ircinia

1

1.4%

Kocuria

1

1.4%

Laceyella

2

2.9%

Lacticaseibacillus

1

1.4%

Lactiplantibacillus

3

4.3%

Lactococcus

1

1.4%

Ligilactobacillus

1

1.4%

Loigolactobacillus

1

1.4%

Lysobacter

1

1.4%

Microbacterium

1

1.4%

Micromonospora

1

1.4%

Nocardiopsis

1

1.4%

Pediococcus

2

2.9%

Providencia

1

1.4%

Pseudomonas

5

7.1%

Pseudovibrio

3

4.3%

Sarcotragus

1

1.4%

Serratia

2

2.9%

Shewanella

1

1.4%

Staphylococcus

2

2.9%

Thermoactinomyces

1

1.4%

Vagococcus

1

1.4%

Table S4. Source of isolation of the biomolecule-producing species.

Source of isolation of the biomolecule-producing species

Number of appearances

Percentage of total

Food

8

16.7%

Marine environment

13

27.1%

Animal or insect

2

4.2%

Data not provided

6

12.5%

Feces

4

8.3%

Soil

8

16.7%

Air

1

2.1%

Cow milk

1

2.1%

Human milk

1

2.1%

Intact human skin

1

2.1%

Compost pile

1

2.1%

Plants

1

2.1%

Shrimp farming tank

1

2.1%

Table S5. Identification methods, nature of the identified bioactive molecule, target species, extraction method used, and cultivation conditions adopted for the production of antibiotic molecules.

N˚

Identification method

Nature of the identified bioactive molecule

Target species (between S. aureus and P. aeruginosa)

Extraction method

Culture medium

Incubation temperature

Incubation time

Shaking during incubation

Oxygen availability during growth

1

Data not provided

Data not provided

S. aureus

Data not provided

TSB broth

37˚C

24 h

No

Aerobiosis

2

CIEX, RPC, LC-MS/MS, SDS-PAGE

Peptide

S. aureus

Precipitation by ammonium sulfate

LB broth

30˚C

24 h

Yes

Aerobiosis

3

CIEX, RPC, LC-MS/MS

Peptide

S. aureus

Precipitation by ammonium sulfate

LB broth

30˚C

24 h

Yes

Aerobiosis

4

HPLC, ESI-MS, RMN

Peptide

S. aureus

Solvent extraction (Methanol)

Data not provided

30˚C

9 days

No

Aerobiosis

5

RMN, MS

Actinomicin D

S. aureus

Silica gel chromatography followed by HPLC

Data not provided

Data not provided

Data not provided

Data not provided

Data not provided

6

LC-HRMS, LC-UV-HRMS

Focoenamycin, Maklamycin

S. aureus

Solvent extraction (acetone)

ATCC-2 broth

28˚C

7 days

Yes

Aerobiosis

7

IEX, RP-HPLC, LC-MS/MS

Peptide

S. aureus

Precipitation by ammonium sulfate

NB broth

30˚C

24 h

Yes

Anaerobiosis

8

Data not provided

Data not provided

S. aureus

Data not provided

TSB broth

28˚C

11 days

Yes

Aerobiosis

9

HPLC-MS, UHPLC-MS

Pyrrolnitrine, pyoluteorin and2,4-diacetylphloroglucinol

S. aureus

Solvent extraction (acetonitrile)

Modified mineral medium and tryptone broth

20˚C

4 - 7 days

Yes

Aerobiosis

10

Data not provided

Data not provided

P. aeruginosa, S. aureus

Data not provided

LB broth

31˚C

48 h

Yes

Aerobiosis

11

Data not provided

Data not provided

S. aureus

Solvent extraction (n-hexane, chloroform, ethyl acetate)

LB broth

30˚C

48 h

No

Aerobiosis

12

GC-MS, FTIR, RMN

Biosurfactant

P. aeruginosa

Solvent extraction (ethyl acetate:Methanol 3:1)

NB broth

37˚C

96 h

Yes

Aerobiosis

13

ESI-MS/MS

Macrolide

S. aureus

Solvent extraction (ethyl acetate, chloroform and methanol), silica gel chromatography

MRS broth

37˚C

72 h

Yes

Aerobiosis

14

RMN

Rifampicin derivatives

S. aureus

Solvent extraction (ethyl acetate and Methanol)

ISP 2 broth

28˚C

Data not provided

Yes

Aerobiosis

15

GC-MS, FTIR, RMN

N-(2-hidroxifenil)-2-fenazinamin

P. aeruginosa, S. aureus

Solvent extraction (ethyl acetate), silica gel chromatographic column

ISP 2 broth

25˚C

7 days

Yes

Aerobiosis

16

SEC, UHPLC-DAD, C18 column

Data not provided

S. aureus

Precipitation by ammonium sulfate

MRS broth

37˚C

24 h

No

Anaerobiosis

17

RP-HPLC, CIEX

Protein

S. aureus

Precipitation by ammonium sulfate

MRS broth

37˚C

36 h

No

Aerobiosis

18

Data not provided

Data not provided

S. aureus

Data not provided

MRS broth

37˚C

24 h

No

Aerobiosis

19

HPLC-MS

Purpuromicin

P. aeruginosa, S. aureus

Solvent extraction (acetone and DMSO)

ATCC-2 broth

28˚C

7 days

Yes

Aerobiosis

20

HPLC-MS, RMN

Grincamycin, angucycline derivatives

S. aureus

Solvent extraction (ethyl acetate, Methanol and hexane) and C18 chromatographic column

Modified broth

30˚C

6 days

Yes

Anaerobiosis

21

Data not provided

Data not provided

P. aeruginosa, S. aureus

Precipitation by ammonium sulfate

BHI broth

30˚C

24 h

Yes

Aerobiosis

22

LC-MS/MS

Proteins

S. aureus

Precipitation by ammonium sulfate

MRS broth

37˚C

24 h

Yes

Anaerobiosis

23

Data not provided

Data not provided

S. aureus

Solvent extraction (ethyl acetate)

BHI broth and Marine broth

25˚C

48 h

No

Aerobiosis

24

LC-MS/MS e RMN

Viridogrisein, griseoviridine

S. aureus

Solvent extraction (Methanol) and C18 column

TSB broth

30˚C

48 h

Yes

Aerobiosis

25

HPLC, GC-MS e RMN

Bacillibatin C derivatives

P. aeruginosa, S. aureus

Solvent extraction (ethyl acetate) and gel chromatographic column

Data not provided

30˚C

36 h

No

Aerobiosis

26

FIA, LC-MS

Data not provided

P. aeruginosa, S. aureus

Solvent extraction (ethyl acetate)

LB broth

30˚C

24 h

Yes

Aerobiosis

27

Cromatografia por coluna, RMN

Protein

P. aeruginosa

Precipitation by ammonium sulfate

Data not provided

Data not provided

24 h

Data not provided

Data not provided

28

UPLC-HR-MS/ MS

Peptide

S. aureus

Solid phase extraction

MB broth

24˚C

48 h

Yes

Aerobiosis

29

Cromatografia por coluna em gel, PAGE

Lysozyme

P. aeruginosa

Precipitation by ammonium sulfate

LB broth

37˚C

24 h

Yes

Aerobiosis

30

UPLC-UV, UPLC-DAD-M S e RMN

Amicoumacins

S. aureus

Diaion HP-20 column and elution with acetone.

Modified Gause broth

28˚C

3 days

Yes

Anaerobiosis

31

UHPLC-MS

Data not provided

S. aureus

Data not provided

MRS broth

37˚C

24 h

Yes

Anaerobiosis

32

SDS-PAGE

Data not provided

S. aureus

Data not provided

LB broth supplemented with tetracycline

30˚C

15 h

No

Aerobiosis

33

FTIR

Surfactin

P. aeruginosa, S. aureus

Precipitation by HCl, Solvent extraction (chloroform and methanol)

MGV broth

45˚C

48 h

Yes

Aerobiosis

34

RP-HPLC, C18 chromatographic column

Fengicin and surfactin

P. aeruginosa, S. aureus

Precipitation by HCl and Solvent extraction (methanol)

LB broth

28˚C

48 h

Yes

Anaerobiosis

35

SDS-PAGE, RP-HPLC

Pentocin

S. aureus

Precipitation by ammonium sulfate

MRS broth

37˚C

20 h

No

Aerobiosis

36

Data not provided

Data not provided

S. aureus

Solvent extraction (ethyl acetate)

MRS broth

37˚C

48 h

No

Aerobiosis

37

SDS-PAGE

Data not provided

S. aureus

Precipitation by ammonium sulfate

LB broth

37˚C

48 h

No

Aerobiosis

38

IEX

Bacteriolisins, tailocins and proteins

S. aureus

Solid phase extraction

Data not provided

Data not provided

Data not provided

Data not provided

Data not provided

39

Data not provided

Data not provided

P. aeruginosa

Data not provided

MRS broth

37˚C

24 h

Yes

Aerobiosis

40

UHPLC-DAD

Bacteriocin

S. aureus

Precipitation by ammonium sulfate,

solid phase extraction

MRS broth and

M17G broth

30˚C

18 h

No

Aerobiosis

41

IEX, RP-HPLC, LC-MS/MS

Bacteriocin

S. aureus

Silica gel chromatography

BHI broth

37˚C

24 h

No

Aerobiosis

42

GC-MS

Cis-vaccenic acid, octadecanoic acid, cholesta-3,5-diene and n-hexadecanoic acid

S. aureus

Solvent extraction (ethyl acetate and Methanol)

ISP 2 broth

28˚C

20 days

Yes

Aerobiosis

43

Data not provided

Bacteriocin

S. aureus

Solvent extraction (ethyl acetate, butanol, hexane, dichloromethane, trichloromethane) and Precipitation by ammonium sulfate

MRS broth

37˚C

18 h

No

Anaerobiosis

44

CCD, HPLC-UV, column chromatography

Data not provided

S. aureus

Data not provided

ISP 2 broth

50˚C

7 days

Yes

Aerobiosis

Table S6. Culture medium applied.

Culture medium applied

Number of appearances

Percentage of total

ATCC-2 Broth

2

4.3%

MRS broth

11

23.4%

LB broth

9

19.1%

Modified mineral medium

1

2.1%

M17G Broth

1

2.1%

Marine broth

1

2.1%

MB broth

1

2.1%

MGV broth

1

2.1%

Modified broth

1

2.1%

Modified Gause Broth

1

2.1%

NB broth

2

4.3%

Tryptone broth

1

2.1%

TSB broth

3

6.4%

ISP2 broth

4

8.5%

BHI broth

3

6.4%

Data not provided

5

10.6%

Table S7. Incubation temperature.

Incubation temperature

Number of appearances

Percentage of total

20˚C

1

2.3%

24˚C

1

2.3%

25˚C

2

4.5%

28˚C

7

15.9%

30˚C

12

27.3%

31˚C

1

2.3%

37˚C

15

34.1%

45˚C

1

2.3%

50˚C

1

2.3%

Data not provided

3

6.8%

Table S8. Incubation time.

Incubation time

Number of appearances

Percentage of total

15 hours

1

2.3%

18 hours

2

4.5%

20 hours

1

2.3%

24 hours

14

31.8%

36 hours

2

4.5%

48 hours

9

20.5%

72 hours

2

4.5%

96 hours

1

2.3%

144 hours

1

2.3%

168 hours

5

11.4%

216 hours

1

2.3%

264 hours

1

2.3%

480 hours

1

2.3%

Data not provided

3

6.8%

Table S9. Usage of shaking during incubation.

Usage of shaking during incubation

Number of appearances

Percentage of total

Yes

26

59.1%

No

15

34.1%

Data not provided

3

6.8%

Table S10. Oxygen availability during growth.

Oxygen availability during growth

Number of appearances

Percentage of total

Aerobiosis

34

77.3%

Anaerobiosis

7

15.9%

Data not provided

3

6.8%

Table S11. Biomolecule extraction methods.

Biomolecule extraction methods

Number of appearances

Percentage of total

Chromatography

9

16.7%

Solid-phase extraction

3

5.6%

Solvent extraction

19

35.2%

Hydrochloric acid precipitation

2

3.7%

Ammonium sulfate precipitation

13

24.1%

Data not provided

8

14.8%

Table S12. Biomolecule identification methods.

Biomolecule identification methods

Number of appearances

Percentage of total

Separation techniques only

20

28.2%

Hybrid techniques

24

33.8%

Spectrometric techniques

3

4.2%

Spectroscopic techniques

10

14.1%

Electrophoretic techniques

5

7.0%

Data not provided

9

12.7%

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

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