# Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not lead to metronidazole resistance.
> Trichomonas vaginalisにおけるフェレドキシン遺伝子の標的置換はメトロニダゾール耐性を引き起こさない


## Abstract

Ferredoxin (Fd) deficiency is frequently observed in metronidazole-resistant Trichomonas vaginalis isolates, leading to the hypothesis that Fd is required for drug activation. To evaluate this directly, a gene replacement system was established in T. vaginalis using a neomycin phosphotransferase marker flanked by Fd genomic sequences. Stable Fd knockout (KO) cells showed complete absence of Fd mRNA and protein. Hydrogenosomal enzyme analysis revealed a fourfold elevation in hydrogenase activity alongside a 95% reduction in pyruvate/ferredoxin oxidoreductase (PFO) activity, while corresponding mRNA levels remained unchanged. Notably, Fd KO cells retained full metronidazole susceptibility under both aerobic and anaerobic conditions. Molecular hydrogen production persisted at approximately 50% of parental levels, indicating that Fd is dispensable for both hydrogen generation and drug activation. These findings suggest the existence of unidentified ferredoxins, flavodoxins, or alternative activation mechanisms independent of PFO and Fd.

### Mechanism

Deletion of the ferredoxin gene reduces PFO activity by 95% and increases hydrogenase activity fourfold, yet metronidazole activation is maintained, implying that unidentified ferredoxins or flavodoxins serve as alternative electron carriers for drug activation independently of canonical PFO-Fd pathways.

## Bibliographic

- **Authors**: Land KM, Delgadillo-Correa MG, Tachezy J, Vanacova S, Hsieh CL, Sutak R, et al.
- **Journal**: Mol Microbiol
- **Year**: 2004
- **PMID**: [14651615](https://pubmed.ncbi.nlm.nih.gov/14651615/)
- **DOI**: [10.1046/j.1365-2958.2003.03791.x](https://doi.org/10.1046/j.1365-2958.2003.03791.x)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: not assessed

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 14651615. https://h2-papers.org/en/papers/14651615
> **Source**: PubMed PMID [14651615](https://pubmed.ncbi.nlm.nih.gov/14651615/)