Antimicrobial Peptide Can Exacerbate Lung Infection in Cystic Fibrosis Patients

An antimicrobial peptide produced by human immune cells may actually promote bacterial survival in cystic fibrosis patients with a chronic lung infection of Pseudomonas aeruginosa and lead to respiratory failure. The discovery was made by Daniel Wozniak and colleagues from Ohio State University Wexner Medical Center, who published a study in PLOS Pathogens.

The work revealed a potential new mechanism of mutagenesis in bacteria — the typical reason for mutagenesis is antibiotic treatment. The peptide known as LL-37, which is produced by polymorphonucleocytes, is canonically known to kill bacteria by disrupting the cell wall when it is present in high concentrations. However, when LL-37 is present in low concentrations, as is the case in the lungs of cystic fibrosis patients, some peptide passes through the bacterial membrane without killing the cells. From there, LL-37 alters the bacterial DNA and mutates the mucA gene by affecting polymerase DinB. This finding was a result of a model of DNA-bound LL-37 that revealed numerous contacts between the two molecules.

When certain genes in Pseudomonas are altered, the bacteria undergo mucoid conversion and produce a thick layer of alginate that makes them more resistant to antibacterial treatments, meaning that when LL-37 mutates mucA, bacteria require higher doses of antimicrobials to be eradicated. This property is not unique to Pseudomonas; the researchers also identified this behavior in Escherichia coli.

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Implications of this work relate to new treatments being developed as alternatives to antimicrobials. Researchers are looking towards cationic antimicrobial peptides, similar to LL-37, due to the thought that they are less susceptible to inducing resistance. However, this study suggests that further consideration of the impact of antimicrobial peptides and the dose at which they are administered is necessary.

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