A antibiotic resistance mechanism that subdues host defences and promotes virulence.

is an important cause of multidrug-resistant infections worldwide. Recent studies highlight the emergence of multidrug-resistant strains which show resistance to colistin, a last-line antibiotic, arising from mutational inactivation of the regulatory gene. However, the precise molecular resistance mechanisms of -associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an gene mutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mutation induces PhoPQ-governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.