Mycoplasmas and oncogenesis: persistent infection and multistage malignant transformation.

Abstract

Oncogenic potential of human mycoplasmas was studied using cultured mouse embryo cells, C3H/10T1/2 (C3H). Mycoplasma fermentans and Mycoplasma penetrans, mycoplasmas found in unusually high frequencies among patients with AIDS, were examined. Instead of acute transformation, a multistage process in promotion and progression of malignant cell transformation with long latency was noted; after 6 passages (1 wk per passage) of persistent infection with M. fermentans, C3H cells exhibited phenotypic changes with malignant characteristics that became progressively more prominent with further prolonged infection. Up to at least the 11th passage, all malignant changes were reversible if mycoplasmas were eradicated by antibiotic treatment. Mycoplasma fermentans and Mycoplasma penetrans are the most common mycoplasmas associated with AIDS (1-3). M penetrans infects male homosexuals and is seroepidemiologically associated with Kaposi sarcoma (4). Wall-free mycoplasmas are among the few prokaryotes that can grow symbiotically and have a close interaction with mammalian cells for long periods of time without causing acute cytopathic effects. Thus, infections in cell culture are commonly unrecognized, and many persistent parasitic infections in humans or in animals are clinically silent (5,6). But what is the potential effect on mammalian hosts parasitically infected by the prokaryotes with seemingly low virulence? Can mycoplasmas, the simplest organisms capable of self-replication, alter significantly and permanently the biological properties of mammalian cells during the long course of persistent infection?In the 1960s, two studies reported that infection of mycoplasmas (Mycoplasma orale and one unspeciated) caused chromosomal changes (7,8). But the studies did not reveal that the cells underwent transformation. A separate study reported that introduction of mycoplasmas into cultures of baby hamster kidney (BHK) cells produced immediate morphological transformation with a higher soft agar cloning efficiency (9). Unfortunately, the BHK cells had a high rate of spontaneous transformation. In the 1980s, one article reported that an arthropod spiroplasma could rapidly transform mouse and monkey cells (10). Most scientists thought mycoplasmas simply introduced confusing artifacts that mimic cell transformation (11).Since the question of whether mycoplasmas can induce malignant transformation of mammalian cells may have great significance in general biology, tumor biology, as well as direct clinical implications, we have examined mycoplasmal transforming effects in the murine embryonic C3H/10T½/2 (C3H) cell system, pne of the few standard test systems available for studying potential carcinogenic agents or factors in animals or humans (12)(13)(14)(15). Using this model system with low inherent spontaneous transformation (12), we did not find mycoplasmas induced acute mammalian cell transformation described in the earlier studies. Instead, we found mycoplasma-mediated oncogenesis had a long latency and required a chronic pe...

Coinfection with Mycoplasma Pneumoniae and Chlamydia Pneumoniae in ruptured plaques associated with acute myocardial infarction

“…Another important point is that mycoplasmas have promitogenic activity 71,72 . On the other hand, a recent study 73 has shown that chlamydial infection inhibits apoptosis in the host cell.…”

Lipoprotein p37 from Mycoplasma hyorhinis inhibiting mammalian cell adhesion

“…Mycoplasma has been associated with many human diseases, such as pneumonitis and urinogenital infections [1][2][3]. Association between mycoplasma, carcinogenesis and metastasis has generally been supported although the underlying mechanism(s) remain an enigma [4][5][6][7][8]. Infectionrelated carcinogenesis, however, has been clearly documented with Helicobacter pylori, bacterium known to induce gastric cancer [9][10].…”

Mycoplasma infection suppresses p53, activates NF-κB and cooperates with oncogenic Ras in rodent fibroblast transformation

“…Similarly, mycoplasmas are common contaminants of laboratory cell cultures that usually do not affect cell growth and therefore remain undetectable in the absence of molecular or immunological assays. However, long-term mycoplasma infections in cell cultures are associated with increased frequency of chromosomal instability and malignant transformation (Tsai et al, 1995;Feng et al, 1999;Cimolai, 2001). Thus, long-term infection with Mycoplasma fermentans or M. penetrans was reported to induce spontaneous transformation of mouse embryo fibroblasts in concert with overexpression of the H-ras and c-myc protooncogenes (Zhang et al, 1997).…”