Within-host novel envZ mutation in Salmonella Enteritidis: Implications for virulence and antibiotic resistance

Within-host adaptation for Salmonella pulmonary infection is poorly studied. In this work, we investigated the evolutionary dynamics of Salmonella enterica serovar Enteritidis (S. Enteritidis) strains sequentially isolated from a patient with chronic pulmonary infections. Notably, isolates from blood, lung and pleural effusion showed variations in virulence and antibiotic resistance. Whole genome sequencing (WGS) and comparative genomics identified an envZ mutation in the pleural effusion isolate, characterized by a novel 15-bp deletion in the transmembrane1 region. Construction of the envZ mutant and in vitro analyses demonstrated that this envZ mutation was associated with reduced growth rates, diminished biofilm formation and decreased survival in the Galleria mellonella infection model. Additionally, the mutation also resulted in increased antibiotic resistance, lower resistance to phagocytosis in RAW264.7 cells, and decreased adherence to bronchial epithelial cells. Moreover, phylogenetic analysis revealed that EnvZ evolution within Enterobacteriaceae was genus specific. In conclusion, our investigation identified a novel mutation site in envZ and demonstrated that it was involved in the adaptation of Salmonella during pulmonary infection.