The Omp85 family protein, TamA, exhibits characteristics of a suitable drug target against Pseudomonas aeruginosa

Duodu, R ORCID: https://orcid.org/0009-0001-1518-9702, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X and Leo, JC ORCID: https://orcid.org/0000-0002-7066-7527, 2026. The Omp85 family protein, TamA, exhibits characteristics of a suitable drug target against Pseudomonas aeruginosa. Microbiology, 172 (4): 001674. ISSN 1350-0872

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Abstract

The outer membrane (OM) of Gram-negative bacteria is crucial for cell stability and virulence and acts as a permeability barrier. The biogenesis, assembly and regulation of proteins in the OM are, therefore, attractive areas of study that could lead to identifying novel drug targets. The translocation and assembly module (TAM), composed of TamA and TamB, facilitates the insertion of some β-barrel proteins into the OM of Escherichia coli and Klebsiella pneumoniae and has also been implicated in lipid homeostasis. However, its role in Pseudomonas aeruginosa remains mostly uncharacterized. To investigate the TAM’s function and drug target potential in P. aeruginosa, we generated both single- and double-gene TAM knockouts and assessed their fitness using competition growth assays against WT strains. The WT significantly outcompeted the TAM mutants, indicating a fitness defect. Proteomic analysis revealed surprisingly similar profiles between WT and the double-knockout strains, while single-knockout strains showed changes in OM proteins and reduced expression of flagellar components consistent with attenuated swimming motility observed in ∆tamA. Single-knockout mutants exhibited differential levels of expression of lipoproteins of the β-barrel assembly machinery, suggesting compensatory OM remodelling. In vivo infection assays using Galleria mellonella larvae demonstrated significantly higher survival rates when infected with TAM mutants, with tamA mutants showing the greatest attenuation in virulence. Our findings demonstrate a role the TAM plays in P. aeruginosa virulence and identify TamA as a potential drug target for the development of new antimicrobial therapies against P. aeruginosa.

Item Type:	Journal article
Publication Title:	Microbiology
Creators:	Duodu, R., Boocock, D.J., Hoyles, L. and Leo, J.C.
Publisher:	Microbiology Society
Date:	21 April 2026
Volume:	172
Number:	4
ISSN:	1350-0872
Identifiers:	Number Type 10.1099/mic.0.001674 DOI 2619472 Other
Rights:	© 2026 the authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	22 Apr 2026 10:29
Last Modified:	22 Apr 2026 10:29
URI:	https://irep.ntu.ac.uk/id/eprint/55586

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