TITLE:
MG289 in Mycoplasma genitalium Enhances Microbial Invasion and Bacterial Persistence in Benign Human Prostate Cells
AUTHORS:
Wasia Rizwani, Leticia Reyes, Jeongsoon Kim, Steve Goodison, Charles J. Rosser
KEYWORDS:
Cancer; ER Stress Proteins; Infection; Mycoplasma genitalium; Prostate; Proteomics
JOURNAL NAME:
Open Journal of Urology,
Vol.3 No.6,
October
4,
2013
ABSTRACT: Introduction: Recent studies suggest that infectious organisms may facilitate
initiation and metastasis of many human cancers. One infectious organism of
interest is Mycoplasma genitalium(Mg),
a prevalent organism in humans known to cause sexually transmitted infection,
as well as urethritis and prostatitis. Previous studies have demonstrated that
benign, non-tumorigenic human prostate cells (BPH-1) chronically exposed to M. genitalium led to the malignant
transformation of these cells as demonstrated in in vitro and in vivo models. Based on work from our laboratory, we felt this malignant
transformation revolved around a specific M.
genitalium’s ABC transporter (MG289) with homology to M. hyorhinis’ ABC
transporter, p37. In this study, differences in M. genitalium’s ability to infect and induce a unique proteome
conducive to tumoral growth were studied with engineered M. genitalium in which the p37 protein was silent. Materials and Methods: Wild-type M. genitalium (strain 431c, designated as M. genitalium WT) and MG289 deficient M. genitalium mutant (strain 260_3, designated as Mg260_3) were
used for this study. We studied the infectivity potential between M. genitalium WT and Mg260_3 upon
exposure to BPH-1 cells. Furthermore, we set out to identify a unique proteome
in BPH-1 cells exposed to M. genitalium WT that could explain its ability to induce malignant transformation of benign
cells. Validation of selected proteomic targets was carried out by Western
blot analysis. Results: Both M. genitalium WT and
Mg260_3 strains showed somewhat similar growth curve when absorbance at 450nm
was matched at day 0. Colony forming units (CFUs) were similar for both strains
at the same absorbance. However, the ability to infect BPH-1 cells was greatly
reduced in Mg260_3 compared to the M. genitalium WT (p Conclusions: In summary, we demonstrate
that Mg260_3, which is deficient of the phosphonate ABC transporter substrate-binding
protein; MG289 (homologue to M. hyorhinis p37), is less effective in invading
and maintaining an intracellular persistence in benign human prostate cells. In
addition, deletion of MG289 resulted in altered BPH-1 responses to M. genitalium infection as evidenced by
differential proteome profiling of BPH-1 infected cells.