Dataset Information

Effect of the Symbiosis with Mycoplasma hominis and Candidatus Mycoplasma Girerdii on Trichomonas vaginalis Metronidazole Susceptibility.

ABSTRACT: Trichomoniasis, the most common non-viral sexually transmitted infection worldwide, is caused by the protozoon Trichomonas vaginalis. The 5- nitroimidazole drugs, of which metronidazole is the most prescribed, are the only effective drugs to treat trichomoniasis. Resistance against metronidazole is increasingly reported among T. vaginalis isolates. T. vaginalis can establish an endosymbiosis with two Mycoplasma species, Mycoplasma hominis and Candidatus Mycoplasma girerdii, whose presence has been demonstrated to influence several aspects of the protozoan pathobiology. The role of M. hominis in T. vaginalis resistance to metronidazole is controversial, while the influence of Ca. M. girerdii has never been investigated. In this work, we investigate the possible correlation between the presence of Ca. M. girerdii and/or M. hominis and the in vitro drug susceptibility in a large group of T. vaginalis isolated in Italy and in Vietnam. We also evaluated, via RNA-seq analysis, the expression of protozoan genes involved in metronidazole resistance in a set of syngenic T. vaginalis strains, differing only for the presence/absence of the two Mycoplasmas. Our results show that the presence of M. hominis significantly increases the sensitivity to metronidazole in T. vaginalis and affects gene expression. On the contrary, the symbiosis with Candidatus Mycoplasma girerdii seems to have no effect on metronidazole resistance in T. vaginalis.

SUBMITTER: Margarita V

PROVIDER: S-EPMC9220282 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of the Symbiosis with Mycoplasma hominis and Candidatus Mycoplasma Girerdii on Trichomonas vaginalis Metronidazole Susceptibility.

Margarita Valentina V Cao Le Chi LC Bailey Nicholas P NP Ngoc Thuy Ha Thi THT Ngo Thi Minh Chau TMC Nu Phuong Anh Ton PAT Diaz Nicia N Dessì Daniele D Hirt Robert P RP Fiori Pier Luigi PL Rappelli Paola P

Antibiotics (Basel, Switzerland) 20220616 6

Trichomoniasis, the most common non-viral sexually transmitted infection worldwide, is caused by the protozoon Trichomonas vaginalis. The 5- nitroimidazole drugs, of which metronidazole is the most prescribed, are the only effective drugs to treat trichomoniasis. Resistance against metronidazole is increasingly reported among T. vaginalis isolates. T. vaginalis can establish an endosymbiosis with two Mycoplasma species, Mycoplasma hominis and Candidatus ...[more]

PMID: 35740218

Similar Datasets

Project description:BackgroundTrichomoniasis caused by Trichomonas vaginalis, combined with its complications, has long frequently damaged millions of human health. Metronidazole (MTZ) is the first choice for therapy. Therefore, a better understanding of its trichomonacidal process to ultimately reveal the global mechanism of action is indispensable. To take a step toward this goal, electron microscopy and RNA sequencing were performed to fully reveal the early changes in T. vaginalis at the cellular and transcriptome levels after treatment with MTZ in vitro.ResultsThe results showed that the morphology and subcellular structures of T. vaginalis underwent prominent alterations, characterized by a rough surface with bubbly protrusions, broken holes and deformed nuclei with decreased nuclear membranes, chromatin and organelles. The RNA-seq data revealed a total of 10,937 differentially expressed genes (DEGs), consisting of 4,978 upregulated and 5,959 downregulated genes. Most DEGs for the known MTZ activators, such as pyruvate:ferredoxin oxidoreductase (PFOR) and iron-sulfur binding domain, were significantly downregulated. However, genes for other possible alternative MTZ activators such as thioredoxin reductase, nitroreductase family proteins and flavodoxin-like fold family proteins, were dramatically stimulated. GO and KEGG analyses revealed that genes for basic vital activities, proteostasis, replication and repair were stimulated under MTZ stress, but those for DNA synthesis, more complicated life activities such as the cell cycle, motility, signaling and even virulence were significantly inhibited in T. vaginalis. Meanwhile, increased single nucleotide polymorphism (SNP) and insertions - deletions (indels) were stimulated by MTZ.ConclusionsThe current study reveals evident nuclear and cytomembrane damage and multiple variations in T. vaginalis at the transcriptional level. These data will offer a meaningful foundation for a deeper understanding of the MTZ trichomonacidal process and the transcriptional response of T. vaginalis to MTZ-induced stress or even cell death.

Project description:Trichomonas vaginalis infections significantly impact public health and are associated with increased likelihood of HIV infection, prostate cancer, and pregnancy complications. Current treatment relies almost exclusively on 5-nitroimidazoles, particularly metronidazole, raising concerns about drug resistance and treatment efficacy. This study is aimed at evaluating the effectiveness of metronidazole and tinidazole on metronidazole-resistant strains of T. vaginalis and at determining whether efflux pump inhibitors could reverse metronidazole resistance. Additionally, the roles of nitroreductases in metronidazole resistance were also studied. Metronidazole and tinidazole were tested on both metronidazole-sensitive and -resistant T. vaginalis strains. A checkerboard assay was conducted to assess the potential synergy between metronidazole or tinidazole and efflux pump inhibitors. Nitroreductase activity and ferric iron reduction assays were employed to study the functions of nitroreductases. Tinidazole demonstrated better effectiveness against metronidazole-resistant strains compared to metronidazole, with lower minimal lethal concentration levels. However, the tested efflux pump inhibitors did not significantly enhance the efficacy of metronidazole or tinidazole. Pyrimethamine showed some activity but did not improve the efficacy of the 5-nitroimidazoles in combination. Investigations into the role of nitroreductases and other enzymes in metronidazole resistance revealed no clear downregulation trend in resistant strains. Notably, nitroreductase 8 was capable of reducing ferric iron. While tinidazole remains a viable alternative for treating metronidazole-resistant T. vaginalis, efflux pump inhibitors do not effectively reverse resistance. The identification of nitroreductase's 8 iron-reducing activity suggests its involvement in metronidazole resistance mechanisms. This finding highlights the need for continued research to develop new treatment strategies and improve the management of trichomoniasis, ultimately reducing its public health burden.

Dataset Information

Effect of the Symbiosis with Mycoplasma hominis and Candidatus Mycoplasma Girerdii on Trichomonas vaginalis Metronidazole Susceptibility.

Publications

Effect of the Symbiosis with <i>Mycoplasma hominis</i> and <i>Candidatus</i> Mycoplasma Girerdii on <i>Trichomonas vaginalis</i> Metronidazole Susceptibility.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets