Wasia Rizwani, Leticia Reyes, Jeongsoon Kim, Steve Goodison, Charles J. Rosser
Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, USA.
Department of Infectious Disease & Pathology, College of Veterinary Medicine, University of Florida, Gainesville, USA.
Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, USA.
Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, USA.
Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, USA.
DOI: 10.4236/oju.2013.36044   PDF    HTML     3,976 Downloads   6,174 Views   Citations

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 < 0.001). This was evident by infectivity assays and confocal microscopy. Proteomic analysis of BPH-1 cells infected with either M. genitalium WT or Mg260_3 for 8 hr, 24 hr and 6 days demonstrated a considerable shift in protein expression over uninfected BPH-1 cells at each time point. The preponderance of perturbed proteins regulated protein synthesis and protein processing, triggering endoplasmic reticulum stress. 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.

Keywords

Cancer; ER Stress Proteins; Infection; Mycoplasma genitalium; Prostate; Proteomics

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Conflicts of Interest

The authors declare no conflicts of interest.

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