Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes
 
 ntr4
 Tv
 
 and
 
 ntr6
 Tv

Paulish-Miller, Teresa E.; Augostini, Peter; Schuyler, Jessica A.; Smith, William L.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.; Secor, W. Evan; Hilbert, David W.

doi:10.1128/aac.02370-13

Cited by 61 publications

(48 citation statements)

References 18 publications

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“…For example, other possible mechanisms were identified, along with the presence of nitroreductase NimA-like genes, which have been implicated in metronidazole resistance in bacteria. In addition, a recent study identified single nucleotide polymorphisms (SNPs) in two nitroreductase genes (ntr4Tv and ntr6Tv) associated with resistance (Paulish-Miller et al, 2014). Consequently, further molecular studies are necessary to establish the exact mechanism of drug resistance in T. vaginalis.Overall, our findings demonstrated a high prevalence of T. vaginalis isolates infected with both M. hominis and different TVVs species.…”

mentioning

confidence: 96%

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

Becker

Santos

Frasson

et al. 2015

Infection, Genetics and Evolution

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Trichomonas vaginalis is the etiological agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in world, with 276.4 million new cases each year. T. vaginalis can be naturally infected with Mycoplasma hominis and Trichomonasvirus species. This study aimed to evaluate the prevalence of T. vaginalis infected with four distinct T. vaginalis viruses (TVVs) and M. hominis among isolates from patients in Porto Alegre city, South Brazil. An additional goal of this study was to investigate whether there is association between metronidazole resistance and the presence of M. hominis during TVV infection. The RNA expression level of the pyruvate ferredoxin oxidoreductase (PFOR) gene was also evaluated among metronidazole-resistant and metronidazole-sensitive T. vaginalis isolates. A total of 530 urine samples were evaluated, and 5.7% samples were positive for T. vaginalis infection. Among them, 4.51% were isolated from female patients and 1.12% were from male patients. Remarkably, the prevalence rates of M. hominis and TVV-positive T. vaginalis isolates were 56.7% and 90%, respectively. Most of the T. vaginalis isolates were metronidazole-sensitive (86.7%), and only four isolates (13.3%) were resistant. There is no statistically significant association between infection by M. hominis and infection by TVVs. Our results refute the hypothesis that the presence of the M. hominis and TVVs is enough to confer metronidazole resistance to T. vaginalis isolates. Additionally, the role of PFOR RNA expression levels in metronidazole resistance as the main mechanism of resistance to metronidazole could not be established. This study is the first report of the T. vaginalis infection by M. hominis and TVVs in a large collection of isolates from South Brazil.

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confidence: 96%

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

Becker

Santos

Frasson

et al. 2015

Infection, Genetics and Evolution

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“…We also observed transcriptional variation in paralogs of superoxide dismutase (SOD; TVAG_039980 down-regulated, TVAG_049140 up-regulated), a family of genes involved in scavenging oxygen reactive species as part of an oxygen defense mechanism in T. vaginalis previously shown to be involved in Mz resistance [24]. Finally, previous studies associated oxygen-insensitive nitroreductase (Ntr) and nitroimidazole reductase (NimA) gene mutations with Mz activation and inactivation, respectively [32,45].…”

Section: Mz Resistance Is Associated With Regulation Of Genes Involvementioning

confidence: 55%

Genetic indicators of drug resistance in the highly repetitive genomes ofTrichomonas vaginalisand other trichomonads

Bradić

Warring

Tooley

et al. 2016

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BackgroundTrichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ~283 million trichomoniasis infections annually and is associated with complications during pregnancy and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but has lead to widespread drug resistance. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. ResultsReduced representation genome sequencings of more than 100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium decays rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in sets of genes for which no function has yet been assigned, as well as in functionallycharacterized genes highly relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase (PFO)).Transcription profiling of these and other genes served as proxy for testing the functional consequences of multiple identified SNPs. Transcription profiles of lab-derived drug resistance strain as well as clinically resistant strain depict common regulation changes in carbohydrate metabolism and oxygen detoxification pathways correlated with Mz resistance. Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly-related species that causes venereal disease in cattle. ConclusionsOur observation of shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggests conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool.

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“…95,96 Recognised problems Sequence variation (e.g., in the cryptic plasmid) may affect sensitivity. 95,96 Recognised problems Sequence variation (e.g., in the cryptic plasmid) may affect sensitivity.…”

Section: Chlamydia Trachomatismentioning

confidence: 99%

“…However, the method is insensitive compared to both culture and NAAT, and requires specific microscopic expertise. 95 Further studies are warranted before molecular methods can be developed to predict T. vaginalis susceptibility to nitroimidazoles so as to inform treatment. Despite its relatively low simplicity, this takes up to 2 days to perform and sensitivity estimates fall well below that of NAAT (approximately 70% 92 ).…”

Section: Diagnosis Of T Vaginalismentioning

confidence: 99%

Opportunities and pitfalls of molecular testing for detecting sexually transmitted pathogens

et al. 2015

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Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes ntr4 _Tv and ntr6 _Tv

Cited by 61 publications

References 18 publications

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

Genetic indicators of drug resistance in the highly repetitive genomes ofTrichomonas vaginalisand other trichomonads

Opportunities and pitfalls of molecular testing for detecting sexually transmitted pathogens

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Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes ntr4 Tv and ntr6 Tv

Cited by 61 publications

References 18 publications

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

High rates of double-stranded RNA viruses and Mycoplasma hominis in Trichomonas vaginalis clinical isolates in South Brazil

Genetic indicators of drug resistance in the highly repetitive genomes ofTrichomonas vaginalisand other trichomonads

Opportunities and pitfalls of molecular testing for detecting sexually transmitted pathogens

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Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes ntr4 _Tv and ntr6 _Tv