Even though LL‑37 is a natural human antimicrobial peptide, the study shows that when it’s present at low, non‑killing levels it can slip into bacteria, stick to their DNA and cause more mutations. This makes some bugs, like Pseudomonas aeruginosa, turn mucoid (a thick protective coating) and become resistant to antibiotics such as rifampicin, which is a concern for chronic infections like cystic fibrosis.

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 [<i>PLoS Pathogens</i> (2014) 10, e1004083] provides evidence that at subinhibitory levels, AMPs promote mutations in bacterial DNA, which enhance bacterial survival. In particular, in the bacterium <i>Pseudomonas aeruginosa,</i> one AMP called LL-37 can promote mutations, which enable the bacteria to overproduce a protective sugar coating, a process called mucoid conversion. <i>P. aeruginosa</i> mucoid 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 both <i>P. aeruginosa</i> and <i>E. coli.</i> This suggests that AMP-induced mutagenesis may be important for a broad range of chronic diseases and pathogens.