LL-37 (Cathelicidin)

The selectivity comes from fundamental differences in membrane composition. Bacterial membranes are predominantly negatively charged phospholipids. LL-37 is positively charged and binds electrostatically to the bacterial membrane. Human cell membranes have neutral outer leaflets (primarily phosphatidylcholine) with higher cholesterol content that reduces membrane fluidity — both factors make them significantly less susceptible to LL-37's pore-forming action.

Yes. Because LL-37 works by physically disrupting the membrane rather than targeting a specific bacterial metabolic enzyme, resistance development is substantially harder than for conventional antibiotics. Bacteria would need to fundamentally alter their membrane composition — a change incompatible with normal function — to resist LL-37's mechanism.

Yes. Topical LL-37 at 0.1-0.5% concentrations has been studied for wound infections, acne, and chronic skin infections. The combination of antimicrobial activity against skin pathogens (Staph aureus, P. acnes) and wound healing promotion makes it particularly appropriate for infected wounds or treatment-resistant skin conditions.

LL-37 has demonstrated cytotoxic activity against multiple cancer cell lines in vitro, including colon, lung, ovarian, and prostate cancers. The mechanism involves membrane disruption and caspase-dependent apoptosis. In vivo mouse tumour models show tumour growth inhibition. This remains active research territory — not an established cancer treatment — but the preclinical evidence is substantive.

Individuals with naturally low LL-37 levels (a subset of the population based on genetic variants) show higher susceptibility to certain bacterial infections, particularly respiratory pathogens. Low LL-37 has also been associated with increased cancer risk in some studies. This provides physiological rationale for supplementation beyond the therapeutic context.

Yes — and often synergistically. LL-37 membrane disruption increases bacterial cell permeability, which can improve the intracellular access of conventional antibiotics. Studies show synergistic minimum inhibitory concentration reductions when LL-37 is combined with antibiotics against MRSA and other resistant pathogens.