The study shows that a type of antibacterial peptide called Bac7 can become less effective against E. coli when the bacteria change certain proteins, but this resistance doesn’t seem to affect other natural peptides like LL‑37. The findings are mostly about how bacteria adapt in the lab, not about how people can use these peptides for health or performance.

Proline-rich antimicrobial peptides (PrAMPs) having a potent antimicrobial activity and a modest toxicity toward mammalian cells attract much attention as new templates for the development of antibiotic drugs. However, a comprehensive understanding of mechanisms of bacterial resistance development to PrAMPs is necessary before their clinical application. In this study, development of the resistance to the proline-rich bovine cathelicidin Bac7_1-22 derivative was characterized in the multidrug-resistant <i>Escherichia coli</i> clinical isolate causing the urinary tract infection. Three Bac7_1-22-resistant strains with &#x2265;16-fold increase in minimal inhibitory concentrations (MICs) were selected by serially passaging after four-week experimental evolution. It was shown that in salt-containing medium, the resistance was mediated by inactivation of the SbmA transporter. The absence of salt in the selection media affected both dynamics and main molecular targets under selective pressure: a point mutation leading to the amino acid substitution N159H in the WaaP kinase responsible for heptose I phosphorylation in the LPS structure was also found. This mutation led to a phenotype with a decreased susceptibility to both the Bac7_1-22 and polymyxin B. Screening of antimicrobial activities with the use of a wide panel of known AMPs, including the human cathelicidin LL-37 and conventional antibiotics, against selected strains indicated no significant cross-resistance effects.