Within-host adaptation mutations associated with persistent colonization ofin a silicosis patient.

is a notorious opportunistic pathogen that causes life-threatening infections in immunocompromised individuals. In this study, we isolated two mucoid imipenem-resistantstrains, SCPa14 and SCPa16, from a single silicosis patient. Whole-genome sequencing revealed that these two strains are homologous, both of which belong to the epidemic high-risk clone ST274. Gene sequence analysis identified a deletion mutation (ΔG 433) of thegene and a premature stop mutation in thegene in SCPa14 and SCPa16; these mutations are assumed to be responsible for their mucoid phenotype and imipenem resistance, respectively. Compared to the reference strain PAO1, both strains showed slow growth, reduced cell motility, increased pyocyanin production, and enhanced HOresistance, which may collectively aid their adaptation to the respiratory tract environment. SCPa14 had impaired biofilm formation, which may be attributed to a premature termination mutation in itsgene. In contrast, SCPa16 exhibited enhanced biofilm formation-a trait that may explain its persistence within the host. However, both strains showed poor growth under iron-restriction stress, which likely results from their lack of pyoverdine genes; they also exhibited impaired resistance to the antimicrobial peptide LL-37 and serum complement. Consistent with these traits, SCPa14 and SCPa16 were identified as low-virulence strains using theinfection experiment. Overall, these data improve understanding of the adaptive strategies and fitness costs ofduring chronic infection in the silicosis patient, which offers new insights for antimicrobial therapy.