Cationic Antimicrobial Peptides Promote Microbial Mutagenesis and Pathoadaptation in Chronic Infections

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Antimicrobial peptides (AMPs) are produced by the mammalian immune system to fight invading pathogens. The best understood function of AMPs is to interact with the membranes of microbes, thereby disrupting and killing cells. However, the amount of AMP available during chronic bacterial infections may not be sufficient to kill pathogens (sub-inhibitory). In this study, we found that at sub-inhibitory levels, AMPs promote mutations in bacterial DNA, a function not previously attributed to them. In particular, we found that in the bacteria Pseudomonas 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. aeruginosa mucoid conversion is a major risk factor for those suffering from cystic fibrosis (CF), the most common lethal, heritable disease in the US. We found that LL-37 is able to produce these mutations by penetrating the bacterial cell and binding to the bacterial DNA. DNA binding disrupts normal DNA replication and allows mutations to occur. Furthermore, we observed LL-37 induced mutagenesis in processes apart from mucoid conversion, in both P. aeruginosa and E. coli. This suggests that AMP-induced mutagenesis may be important for a broad range of chronic diseases and pathogens.

Vyšlo v časopise: Cationic Antimicrobial Peptides Promote Microbial Mutagenesis and Pathoadaptation in Chronic Infections. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004083
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004083

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