title: Mutagenesis by host antimicrobial peptides: insights into microbial evolution during chronic infections.
abstract: Antimicrobial peptides (AMPs) are produced by the mammalian immune system to fight invading pathogens. The best understood function of AMPs is to integrate into the membranes of microbes, thereby disrupting and killing cells. However, a recent study [PLoS Pathogens(2014) 10, e1004083] provides evidence that at subinhibitory levels, AMPs promote mutations in bacterial DNA, which enhance bacterial survival. In particular, in the bacteriumPseudomonas aeruginosa,one AMP called LL-37 can promote mutations, which enable the bacteria to overproduce a protective sugar coating, a process called mucoid conversion.P. aeruginosamucoid conversion is a major risk factor for those suffering from cystic fibrosis (CF), one of the most common lethal, heritable diseases in the US. LL-37 was found to produce mutations by penetrating the bacterial cell and binding to bacterial DNA. It was proposed that LL-37 binding DNA disrupts normal DNA replication and potentiates mutations. Importantly, LL-37 induced mutagenesis was also found to promote resistance to rifampicin in bothP. aeruginosaandE. coli.This suggests that AMP-induced mutagenesis may be important for a broad range of chronic diseases and pathogens.
authors.affiliation: Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA.
authors.forename: Dominique H
authors.initials: DH
authors.lastname: Limoli
authors.affiliation: Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wozniak
keywords: DNA repair; Pseudomonas aeruginosa; antimicrobial peptides; cystic fibrosis; mutagenesis