SPLUNC1 (short palate lung and nasal epithelial clone 1) is a multifunctional
host defense protein found in human respiratory tract with antimicrobial
properties. In this work, we compare the biological activities of
four SPLUNC1 antimicrobial peptide (AMP) derivatives using paired
clinical isolates of the Gram-negative (G(−)) bacteriaKlebsiella pneumoniae, obtained from 11 patients
with/without colistin resistance. Secondary structural studies were
carried out to study interactions between the AMPs and lipid model
membranes (LMMs) utilizing circular dichroism (CD). Two peptides were
further characterized using X-ray diffuse scattering (XDS) and neutron
reflectivity (NR). A4-153 displayed superior antibacterial activity
in both G(−) planktonic cultures and biofilms. NR and XDS revealed
that A4-153 (highest activity) is located primarily in membrane headgroups,
while A4-198 (lowest activity) is located in hydrophobic interior.
CD revealed that A4-153 is helical, while A4-198 has little helical
character, demonstrating that helicity and efficacy are correlated
in these SPLUNC1 AMPs.