Metabolic cooperation supports mutual growth between the protozoan parasite Trichomonas vaginalis and dysbiotic vaginal bacteria
- 1School of Biological Sciences, University of Auckland, Auckland, New Zealand
Abstract
The protozoan parasite Trichomonas vaginalis, the causative agent of trichomoniasis, is frequently associated with dysbiotic vaginal microbial communities characteristic of bacterial vaginosis (BV). While previous studies have shown that vaginal bacteria can modulate parasite pathogenicity, the metabolic basis underlying this ecological association remains unclear. Here, we investigated whether T. vaginalis and BV-associated bacteria (BVAB) engage in metabolic cooperation that could support their coexistence. Using in vitro co-culture systems, we examined microbial growth under defined nutrient conditions and integrated metabolomic profiling with targeted transcriptional analysis to characterize metabolic interactions between partners. In serum-free defined medium that does not support proliferation of either microorganism alone, T. vaginalis and BVAB exhibited mutualistic growth, indicating that they engage in cooperative metabolic interactions to overcome shared nutritional limitations. Gas chromatography-mass spectrometry revealed a coordinated metabolic shift toward amino acid catabolism during co-culture, with prominent accumulation of ornithine and putrescine linking the arginine dihydrolase (ADH) pathway to polyamine synthesis. Gene expression analyses showed strong upregulation of the parasite carbamate kinase gene during co-culture, implicating enhanced ADH pathway activity in this interaction. Inhibition of polyamine biosynthesis partially impaired the cooperative growth of both microorganisms, further supporting the importance of this metabolic axis. Together, these findings provide experimental evidence that cross-kingdom metabolic cooperation can reciprocally support infection and dysbiosis, highlighting how parasite-microbiome interactions can reshape metabolic networks to overcome environmental constraints and promote their persistence within host-associated microbial ecosystems. Author summary: Pathogens rarely occur in isolation. Instead, they interact with other microorganisms that inhabit the same host environment, forming complex communities that can influence disease outcomes. The sexually transmitted protozoan parasite Trichomonas vaginalis is strongly associated with bacterial vaginosis (BV), a common imbalance of the vaginal microbiome characterized by the overgrowth of some anaerobic bacteria. However, the biological basis for this association has remained unclear. In this study, we investigated whether the parasite and these bacteria can support each other’s growth through metabolic cooperation. Using laboratory co-culture systems, we found that T. vaginalis and BV-associated bacteria can grow together under nutrient conditions that prevent either organism from growing alone. Metabolomic analyses revealed that this cooperative growth is accompanied by a shift toward amino acid metabolism and the accumulation of metabolites involved in alternative energy production and polyamine synthesis. Blocking polyamine production impaired the growth of both organisms in co-culture, indicating that this pathway contributes to their interaction. These findings suggest that metabolic cooperation between pathogen and dysbiotic bacteria may favour infection and help stabilize vaginal dysbiosis. More broadly, our work highlights the importance of studying infections within their microbial context, where interactions between pathogens and bacteria can shape community structure and impact on severity and persistence of disease.
Related
- Characterization of the N7 RNA cap methyltransferase from Trichomonas vaginalis and inhibitor discovery
- The mannose 6-phosphate receptor system is ancient, widespread in eukaryotes, and functionally diversified in the human parasite Trichomonas vaginalis
- Stop codon readthrough in Trichomonas is a mechanism for gene expression regulation and expanding protein function
- Metabolic Remodeling in Peritoneal Dialysis-Associated Peritoneal Fibrosis: Mechanisms, Candidate Metabolic Signatures, and Therapeutic Perspectives
- Metabolic reprogramming and metabolic homeostasis in podocyte injury: novel mechanistic insights and natural product therapies
BibTeX
@article{hinderfeld2026metabolic,
title = {{Metabolic cooperation supports mutual growth between the protozoan parasite Trichomonas vaginalis and dysbiotic vaginal bacteria}},
author = {Annabel S. Hinderfeld and Raphael Bang and Bailey S. Dickson and Saif Faraj and Augusto Simoes-Barbosa},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014620},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014620},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metabolic cooperation supports mutual growth between the protozoan parasite Trichomonas vaginalis and dysbiotic vaginal bacteria
AU - Annabel S. Hinderfeld
AU - Raphael Bang
AU - Bailey S. Dickson
AU - Saif Faraj
AU - Augusto Simoes-Barbosa
PY - 2026
DA - 2026/09/23
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014620
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014620
AB - The protozoan parasite Trichomonas vaginalis, the causative agent of trichomoniasis, is frequently associated with dysbiotic vaginal microbial communities characteristic of bacterial vaginosis (BV). While previous studies have shown that vaginal bacteria can modulate parasite pathogenicity, the metabolic basis underlying this ecological association remains unclear. Here, we investigated whether T. vaginalis and BV-associated bacteria (BVAB) engage in metabolic cooperation that could support their coexistence. Using in vitro co-culture systems, we examined microbial growth under defined nutrient conditions and integrated metabolomic profiling with targeted transcriptional analysis to characterize metabolic interactions between partners. In serum-free defined medium that does not support proliferation of either microorganism alone, T. vaginalis and BVAB exhibited mutualistic growth, indicating that they engage in cooperative metabolic interactions to overcome shared nutritional limitations. Gas chromatography-mass spectrometry revealed a coordinated metabolic shift toward amino acid catabolism during co-culture, with prominent accumulation of ornithine and putrescine linking the arginine dihydrolase (ADH) pathway to polyamine synthesis. Gene expression analyses showed strong upregulation of the parasite carbamate kinase gene during co-culture, implicating enhanced ADH pathway activity in this interaction. Inhibition of polyamine biosynthesis partially impaired the cooperative growth of both microorganisms, further supporting the importance of this metabolic axis. Together, these findings provide experimental evidence that cross-kingdom metabolic cooperation can reciprocally support infection and dysbiosis, highlighting how parasite-microbiome interactions can reshape metabolic networks to overcome environmental constraints and promote their persistence within host-associated microbial ecosystems. Author summary: Pathogens rarely occur in isolation. Instead, they interact with other microorganisms that inhabit the same host environment, forming complex communities that can influence disease outcomes. The sexually transmitted protozoan parasite Trichomonas vaginalis is strongly associated with bacterial vaginosis (BV), a common imbalance of the vaginal microbiome characterized by the overgrowth of some anaerobic bacteria. However, the biological basis for this association has remained unclear. In this study, we investigated whether the parasite and these bacteria can support each other’s growth through metabolic cooperation. Using laboratory co-culture systems, we found that T. vaginalis and BV-associated bacteria can grow together under nutrient conditions that prevent either organism from growing alone. Metabolomic analyses revealed that this cooperative growth is accompanied by a shift toward amino acid metabolism and the accumulation of metabolites involved in alternative energy production and polyamine synthesis. Blocking polyamine production impaired the growth of both organisms in co-culture, indicating that this pathway contributes to their interaction. These findings suggest that metabolic cooperation between pathogen and dysbiotic bacteria may favour infection and help stabilize vaginal dysbiosis. More broadly, our work highlights the importance of studying infections within their microbial context, where interactions between pathogens and bacteria can shape community structure and impact on severity and persistence of disease.
SN - 1553-7374
ER -