Colistin-induced transition from non-mucoid to mucoid phenotype in resistantST3351.

Abstract

is an opportunistic pathogen frequently infecting the lower airways of individuals with cystic fibrosis (iwCF). We investigated colistin (CST) resistance mechanisms inST3351 (-ST3351) and their impact on bacterial virulence.-ST3351, a novel CST-resistant sequence type, was isolated from a child with CF. We demonstrate that CST resistance in-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-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-ST3351 may contribute to disease progression in iwCF, particularly when CST resistance and mucoid conversion remain undetected during CST nebulized therapy.