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. 2022 Jun 16;11(6):812.
doi: 10.3390/antibiotics11060812.

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

Valentina Margarita  1 , Le Chi Cao  2 , Nicholas P Bailey  3 , Thuy Ha Thi Ngoc  2 , Thi Minh Chau Ngo  2 , Phuong Anh Ton Nu  2 , Nicia Diaz  1 , Daniele Dessì  1   4 , Robert P Hirt  3 , Pier Luigi Fiori  1   4 , Paola Rappelli  1   4
Affiliations

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

Valentina Margarita et al. Antibiotics (Basel). .

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.

Keywords: Candidatus Mycoplasma girerdii; Mycoplasma hominis; RNA-seq; Trichomonas vaginalis; metronidazole; resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The impact of M. hominis and ‘Ca. M. girerdii’ presence on sensibility of metronidazole of T. vaginalis isolates. Statistical significance was tested via Student’s t-test. Tv = T. vaginalis, Mh = M. hominis, Mg = Ca. M. girerdii. M. hominis positive strains are associated with an increase of sensitivity to metronidazole compared to M.hominis free strains, independently from the presence of Mg (* p < 0.01).
Figure 2
Figure 2
The metronidazole susceptibility of T. vaginalis isogenic strains. The mean values of metronidazole MLC for T. vaginalis experimentally (iSS62-Mh+Mg−, iSS62-Mh+Mg+) and naturally Mycoplasma-infected (iSS62-Mh−Mg+), and for Mycoplasma-free T. vaginalis (iSS62-Mh−Mg−), were compared. The presence of M. hominis in trichomonad cells is associated with an increase of sensitivity to metronidazole compared to iTv, independently from the presence of Mg (* p < 0.05). Statistical significance was tested by Student’s t-test.
Figure 3
Figure 3
The differential expression of selected T. vaginalis genes related to metronidazole resistance alone and in association with M. hominis or with Ca. M. girerdii. Expression units are z-scaled trimmed mean of M-values (TMM). * Indicates genes with a statistically significant difference of expression between Mycoplasma-free T. vaginalis iSS62-Mh−Mg− (Tv) and T. vaginalis associated with M. hominis iSS62-Mh+Mg− (Tv-Mh).
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