MG289 in <i>Mycoplasma genitalium</i>Enhances Microbial Invasion and Bacterial Persistence in Benign Human Prostate Cells

• 作者: Charles J. Rosser Jeongsoon Kim Leticia Reyes Steve Goodison Wasia Rizwani
• 来源期刊: 泌尿学期刊(英文)
• 学科: 医学
• 关键词: Cancer ER Stress Proteins Infection MYCOPLASMA genitalium PROSTATE Proteomics
• 年，卷（期）: mnxqkyw_2013,（6）
• 页码范围: 232-245
• 页数: 14页
• 分类号: R73

摘要

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