Work

Strain-specific variation in the complement resistome of Pseudomonas aeruginosa

Year: 2025

Type: article

Abstract: ABSTRACT Bloodstream infections caused by Pseudomonas aeruginosa are associated with high mortality rates. The complement system, a key component of the innate immune response, plays a major role in eliminating P. aeruginosa from human blood. However, the sensitivity of P. aeruginosa strains to plasma varies widely, ranging from highly sensitive to persistent or fully resistant. Although most studies use model strains, the species genomic and phenotypic diversities suggest more complex interactions with complement than previously appreciated. In this study, we characterized the plasma resistome of P. aeruginosa using Tn-seq in three strains with varying levels of plasma sensitivity. A gain-of-function screen in the plasma-sensitive strain PA14 revealed numerous bacterial factors influencing plasma resistance, including components of the RetS-LadS/Gac/Rsm regulatory pathway and outer membrane porins. In the plasma-resistant strains CHA and YIK, Tn-seq analysis indicated that each strain relies on a distinct, limited set of proteins to evade complement-mediated killing. Despite these differences, we identified common mechanisms across all three strains. These include the production of exopolysaccharides (EPSs), the presence of surface appendages, and modifications in the O-specific antigen. Notably, we identified Ssg and Crc as shared contributors to plasma resistance. Although deletion mutants lacking ssg and/or crc exhibited reduced survival in plasma, a subpopulation of these mutants was able to persist during prolonged exposure. Overall, this work provides new insights into the complex interplay between P. aeruginosa and the human complement system in the context of bloodstream infections and raises concerns regarding the efficacy of therapies that target individual virulence factors.

Source: Infection and Immunity

DOI: 10.1128/iai.00055-25

Authors: Manon Janet-Maitre, Myène Robert-Genthon, François Cretin, Sylvie Elsen, Ina Attrée

Institutions: Institut de Biologie Structurale, Université Grenoble Alpes

Language: English

Topic: Bacterial biofilms and quorum sensing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Agence Nationale de la Recherche, Fondation pour la Recherche Médicale