Colistin-induced transition from non-mucoid to mucoid phenotype in resistant Pseudomonas aeruginosa ST3351
Year: 2025
Type: article
Abstract: Pseudomonas aeruginosa is an opportunistic pathogen frequently infecting the lower airways of individuals with cystic fibrosis (iwCF). We investigated colistin (CST) resistance mechanisms in P. aeruginosa ST3351 (Psa-ST3351) and their impact on bacterial virulence. Psa-ST3351, a novel CST-resistant sequence type, was isolated from a child with CF. We demonstrate that CST resistance in Psa-ST3351 depends on the addition of 4-amino-4-deoxy-L-arabinose to lipid A. Moreover, exposure to CST induced a non-mucoid-to-mucoid phenotypic switch characterized by enhanced swarming motility, decreased susceptibility to aminoglycosides, impaired ExoS secretion via the type-III secretion system, and increased bacterial competition, all hallmarks of a chronic infection phenotype. CST-treated Psa-ST3351 also exhibited reduced phagocytosis by macrophages, despite the induction of pro-inflammatory cytokines remaining unaffected, and enhanced the pathogenicity in a mouse pneumonia model. These findings suggest that CST-induced mucoid conversion in CST-resistant Psa-ST3351 May contribute to disease progression in iwCF, particularly when CST resistance and mucoid conversion remain undetected during CST nebulized therapy.
Source: Virulence
Authors: Roberto Rosales-Reyes, Verónica Roxana Flores-Vega, Miguel A. Ares, Guanbo Wang, Luis Fernando Montelongo-Martínez, Ramón G. Varela-Nájera, Miguel A. de la Cruz, Guilherme E. Paiva, Marco Elias Gudiño-Zayas, Gabriela Hernández-Martínez, Nilton Lincopan, Miguel Cocotl-Yañez, Araceli Pérez-López, Thelma Rizo-Pica, José Luis Lezana-Fernandez, Vianney Ortiz-Navarrete, Santiago Partida-Sanchez, María Dolores Alcántar-Curiel, Miguel A. Valvano, José Ignacio Santos-Preciado
Institutions: Universidad Nacional Autónoma de México, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexican Social Security Institute, Queen's University Belfast, Benemérita Universidad Autónoma de Puebla, Universidade de São Paulo, Hospital General de México, Hospital Infantil de México Federico Gómez, Nationwide Children's Hospital, Abigail Wexner Research Institute, The Ohio State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,557
Funder: Cystic Fibrosis Foundation
Award: G6343834429
OpenAlex ID: W4415595801
