"Biomolecular Approaches to Trichomoniasis: Epidemiology, Diagnosis, and Treatment"

Alexandra Ibáñez-Escribano^1*Tiana Tasca^2*Valentina Margarita^3*

• ¹Department of Microbiology and Parasitology, Complutense University of Madrid, Madrid, Spain
• ²Universidade Federal do Rio Grande do Sul, Faculdade de Farmácia and Centro de Biotecnologia, Porto Alegre, RS, Brazil
• ³Department of Biomedical Science, Universita degli Studi di Sassari, Sassari, Italy

Frontiers in Parasitology Editorial Research Topic "Biomolecular Approaches to Trichomoniasis: Epidemiology, Diagnosis, and Treatment" Alexandra Ibáñez-Escribano, Tiana Tasca, Valentina Margarita Trichomoniasis is a significant public health concern, particularly due to its adverse effects during pregnancy and its established role in facilitating the acquisition of other sexually transmitted infections, as well as in the development of prostate and cervical cancers. Despite being classified by the Centers for Disease Control and Prevention as a Neglected Parasitic Infection, recent molecular and biological advancements have greatly enhanced our understanding of this protozoan. The latest World Health Organization (WHO) report on global health sector strategies on STIs (2022–2030), which aims to reduce new STI cases by 50% by 2030, highlights the urgency of addressing this pathogen, particularly in the context of increasing treatment resistance. This topic brings together the latest research on Trichomonas vaginalis, with a focus on its virulence, the identification on therapeutic targets, and the development of effective treatment strategies. The article by Aranda-Chan et al. (https://doi.org/10.3389/fpara.2025.1512012) shows the role of trichocystatin 2 (TC-2) as potential biomarker. TC-2 has been previously identified as one of the three endogenous inhibitors of the parasite's cathepsin L-like cysteine-proteases. TC-2 inhibits the activity of papain and cathepsin L as well as the proteolytic activity of T. vaginalis protease-resistant extracts and was even able to protect HeLa cell monolayers from cytotoxic damage caused by the parasite. The challenge showed in this work regards to solve the production of multimeric aggregates when TC-2 is recombinantly expressed in E. coli, which could impair its stability and production in larger scale and longer production time. Considering that TC-2 possesses five cysteines, including four located at the N-terminus, these cysteines are proposed to promote the formation of recombinant TC-2 multimers. In this study a recombinant TC-2 mutant was expressed, purified, characterized, and compared with the recombinant wild-type TC-2 protein. The results showed that the four cysteines located in the N-terminal region are responsible for aggregation, and their deletion affected the interaction of TC-2 with papain without affecting its inhibitory activity on homologous target proteases that are crucial for T. vaginalis virulence, suggesting TC-2 as a potential therapeutic target. Likewise, continuing with the study of certain molecules of the parasite as potential biomarkers, the research conducted by Euceda-Padilla et al. (https://doi.org/10.3389/fpara.2025.1546468) was focused on the cysteine peptidases TvLEGU-1 and TvLEGU-2 present in the vaginal secretions of infected women. Cysteine peptidases are an extensive group of proteins, some of them contributing to the parasite´s pathogenesis. Considering the glucose fluctuations observed in the vagina and during trichomoniasis, the effect of glucose on these two biomarkers was evaluated in vitro. The results suggest that both TvLEGU-1 and TvLEGU-2 are secreted in different vesicles, in a time-dependent manner and play an important role during T. vaginalis infection under different glucose conditions. The In vitro co-culture model of Trichomonas vaginalis, Candida albicans, and Lactobacillus crispatus by Cardoso et al. (https://doi.org/10.3389/fpara.2025.1523113) was published in this Research Topic, demonstrating a system for assessing antimicrobial activity and microorganism interactions in vaginitis. In this study the authors established an in vitro co-culture of Trichomonas vaginalis, Candida albicans, and Lactobacillus crispatus to simulate the vaginal microenvironment at the site of infection. Man-Rogosa-Sharpe broth (MRS) medium was chosen for the co-culture, with initial cell densities determined as trophozoites counting in hemocytometer and colony-forming units (CFU) on selective agar for C. albicans and L. crispatus. The co-culture system demonstrated lower MIC values for standard treatments such as metronidazole and fluconazole. Furthermore, the triple co-culture increased the T. vaginalis cytotoxicity to vaginal cell and erythrocytes while significantly inhibited both biofilm formation and metabolic activity of C. albicans, as well as its yeast-to-hyphae transition. This co-culture system is a valuable tool for evaluating the antimicrobial efficacy of novel compounds against vaginitis pathogens and for studying interactions within the vaginal microenvironment. In the context of exploring novel pharmacological alternatives, Margarita et al. (https://doi.org/10.3389/fpara.2025.1610965) investigated the trichomonacidal activity of essential oils (EO) from Cymbopogon citratus, Citrus grandis, and Mentha arvensis, as well as their effects on the two endobiont bacteria harbored by Trichomonas vaginalis: Mycoplasma hominis and Candidatus Mycoplasma girerdii. The study assessed the effect of these extracts against 30 T. vaginalis isolates, both with and without micoplasma endobionts, and with varying levels of metronidazole susceptibility. Among the tested EO, C. citratus displayed the most consistent activity across all isolates. Importantly, none of the extracts exhibited unspecific cytotoxicity on mammalian cells or disrupted the vaginal microbiota. These findings highlight the potential of medicinal plants as valuable sources of effective and safe alternatives against T. vaginalis while preserving vaginal health. In summary, recent advances have highlighted promising directions for the diagnosis and treatment of trichomoniasis. Novel biomarkers such as TC-2 and TvLEGU-1 and TvLEGU-2 provide new insights into parasite virulence and host interactions. TC-2 can be used as potential therapeutic target since it was identified as a regulator of cysteine-protease activity, protecting host cells from T. vaginalis cytotoxicity. TvLEGU-1 and TvLEGU-2, previously characterized as immunogenic and found in the vaginal secretions of patients with trichomoniasis, were also secreted in vitro under the influence of glucose in a time-dependent manner and show proteolytic activity. These findings support their involvement to parasite pathogenesis, reinforcing their diagnostic and therapeutic relevance. Host-pathogen-microbiota interactions were also investigated through an innovative in vitro co-culture model involving T. vaginalis, C. albicans and L. crispatus, mimicking the vaginal environment. The system demonstrated lower MIC values for standard treatments compared to monocultures of T. vaginalis and C. albicans, with an increment of protozoan cytotoxicity against vaginal cells and erythrocytes. Inhibition both biofilm formation and metabolic activity of C. albicans together with yeast-to-hyphae transition were also observed. These data support underscore the development of in vitro co-culture system for testing antimicrobial efficacy under physiologically relevant conditions. In parallel, natural product–based strategies, particularly the use of essential oils, was evaluated as alternative treatment for trichomoniasis. The novel of this research was assessing the influence of M. hominis and Ca. M. girerdii on T. vaginalis susceptibility to essential oils. All three essential oils exhibited effective antitrichomonal activity, with C. citratus oil exhibiting the strongest inhibitory effect on T. vaginalis, including strains harboring bacterial symbionts, and maintaining safety for host cells and the vaginal microbiota. Collectively, these findings emphasize the importance of integrating molecular biomarkers, advanced experimental models, and novel therapeutic approaches to advance future strategies against T. vaginalis.