The protozoanTrichomonas vaginalistargets bacteria with laterally-acquired NlpC/P60 peptidoglycan hydrolases

Abstract

Trichomonas vaginalis is a human eukaryotic pathogen and the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. This extracellular protozoan parasite is intimately associated with the human vaginal mucosa and microbiota but key aspects of the complex interactions between the parasite and the vaginal bacteria remain elusive. We report that T. vaginalis has acquired, by lateral gene transfer from bacteria, genes encoding peptidoglycan hydrolases of the NlpC/P60 family. Two of the T. vaginalis enzymes were active against bacterial peptidoglycan, retaining the active site fold and specificity as DL-endopeptidases. The endogenous NlpC/P60 genes are transcriptionally up regulated in T. vaginalis when in the presence of bacteria. The over-expression of an exogenous copy produces a remarkable phenotype where the parasite is capable of competing out bacteria from mixed cultures, consistent with the biochemical activity of the enzyme in vitro. Our study highlights the relevance of the interactions of this eukaryotic pathogen with bacteria, a poorly understood aspect on the biology of this important human parasite.Author summaryTrichomonas vaginalis is a protozoan parasite that causes a very common sexually transmitted disease known as trichomoniasis. This extracellular parasite resides in the vagina where it is in close association with the mucosa and the local microbiota. Very little is known about the nature of the parasite-bacteria interactions. Here, we report that this parasite had acquired genes from bacteria which retained their original function producing active enzymes capable of degrading peptidoglycan, a polymer that is chemically unique to the cell envelope of bacteria. Our results indicate that these enzymes help the parasite compete out bacteria in mixed cultures. These observations suggest that these enzymes may be critical for the parasite to establish infection in the vagina, a body site that is densely colonised with bacteria. Our study further highlights the importance of understanding the interactions between pathogens and microbiota, as the outcomes of these interactions are increasingly understood to have important implications on health and disease.

Mucosal microbial parasites/symbionts in health and disease: an integrative overview

“…Dysbiosis associated with infections by T. vaginalis is also thought to contribute to the pathobiology of T. vaginalis (Fichorova et al ., 2017; Mercer and Johnson, 2018). Direct targeting of bacteria peptidoglycans by the parasite through enzymes of bacterial origins (Pinheiro et al ., 2018) could potentially contribute to modulate the microbiota bacterial taxonomic composition in addition to contributing to T. vaginalis capacity to colonize the mucosal surface. The combination of the parasite and several bacterial species characteristic of dysbiotic vaginal microbiota associated with trichomoniasis, were also recently shown to synergistically affect the integrity of the tight junction complex of the cervicovaginal epithelial cells (Hinderfeld et al ., 2019).…”

An NlpC/P60 protein catalyzes a key step in peptidoglycan recycling at the intersection of energy recovery, cell division and immune evasion in the intracellular pathogenChlamydia trachomatis

“…[44]. These data indicate that our understanding of substrate binding in prokaryotic NlpC/P60 proteins is not yet fully established.…”