Klebsiella pneumoniae is becoming increasingly difficult to treat as multidrug-resistant (MDR) strains become more prevalent. The formation of biofilm heightens this threat by embedding bacterial cells in a polysaccharide-rich matrix that limits antibiotic penetration. Here we dissect the anti-biofilm bovine host-defense cathelicidin peptide fragment bac7 (1–35), exploring its anti-biofilm mechanism, evaluating its ability to curb colonization of the vital organs by hypervirulent K. pneumoniae , and testing its breadth of activity against diverse clinical isolates. Transcriptomic profiling revealed that bac7 (1–35) simultaneously compromises the bacterial membrane and inhibits ribosomal function, a dual assault that precipitates rapid biofilm collapse and blocks bacterial spread. Further, bac7 (1–35) eradicated the strongest biofilms produced by MDR clinical isolates in the Multidrug-Resistant Organism Repository and Surveillance Network (MRSN) diversity panel. Although bac7 (1–35) kills bacterial cells via a cytosolic mechanism, membrane interaction profiles varied among MRSN isolates, correlating with differential peptide translocation. In a delayed-treatment murine skin-abscess model, bac7 (1–35) halted in vivo colonization of the vital organs by the hypervirulent strain NTUH-K2044. Collectively, these results delineate a multifaceted mode of action for bac7 (1–35) and underscore its therapeutic promise against biofilm-associated MDR K. pneumoniae infections.
Martínez et al. (2025) studied this question.