<i>Pseudomonas aeruginosa lasR</i> -deficient mutant contributes to bacterial virulence through enhancing the PhoB-mediated pathway in response to host environment

<i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that causes life-threatening infections. The bacterial quorum-sensing systems play important roles in coordinating gene expression during infection. Loss-of-function mutations in a quorum-sensing regulator gene <i>lasR</i> are commonly found in clinical isolates, which are associated with more rapid lung function decline. Here, in a murine cutaneous abscess model, we demonstrate that the presence of a <i>lasR</i>-defective mutant results in hyperproduction of virulence factors, increased antibiotic resistance, and more severe tissue damage, which resembles the human circumstance. We further identify the host environment signal and a novel regulatory pathway whereby mutation of <i>lasR</i> increases the bacterial pathogenesis. Our findings offer new insights into the LasR-mediated regulatory network in response to the host environment and provide clues to understand the lung disease progression driven by <i>lasR</i>-defective mutants.