# Using a high-throughput, whole-cell hydrogenase assay to identify potential small molecule inhibitors of [NiFe]-hydrogenase.
> ハイスループット全細胞アッセイを用いた[NiFe]-ヒドロゲナーゼの小分子阻害剤候補の探索


## Abstract

Several human pathogens rely on [NiFe]-hydrogenases to reversibly interconvert molecular hydrogen with protons and electrons, gaining metabolic flexibility in anaerobic environments. Because the nickel insertion pathway required for functional enzyme assembly is absent in human biochemistry, it represents an attractive antimicrobial target. Using Escherichia coli as a model, this study examined nickel availability for hydrogenase production and activity via immunoblot and enzymatic assays. A high-throughput whole-cell screen against a library of known bioactive compounds identified iodoquinol as a candidate inhibitor of the nickel biosynthetic pathway. However, subsequent immunoblot experiments revealed confounding effects that varied with the bacterial growth phase, underscoring the importance of accounting for growth phenotype when interpreting whole-cell assay data related to metal trafficking and cellular homeostasis.

### Mechanism

Blocking the nickel insertion pathway prevents assembly of functional [NiFe]-hydrogenase, thereby disrupting the pathogen's ability to utilize molecular hydrogen as an energy source in anaerobic conditions.

## Bibliographic

- **Authors**: Sebastiampillai S, Lacasse MJ, McCusker S, Campbell T, Nitz M, Zamble DB
- **Journal**: Metallomics
- **Year**: 2022 (2022-10-08)
- **PMID**: [36190308](https://pubmed.ncbi.nlm.nih.gov/36190308/)
- **DOI**: [10.1093/mtomcs/mfac073](https://doi.org/10.1093/mtomcs/mfac073)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: mixed

## 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 36190308. https://h2-papers.org/en/papers/36190308
> **Source**: PubMed PMID [36190308](https://pubmed.ncbi.nlm.nih.gov/36190308/)