Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria.
Tanvi Jakkampudi, Qiao Lin, Saheli Mitra, Aishwarya Vijai, Weiheng Qin, Ann Kang, Jespar Chen, Emma Ryan, Runxuan Wang, Yuqi Gong, Frank Heinrich, Junming Song, Yuan-Pu Peter Di, Stephanie Tristram-Nagle
Author Information
Tanvi Jakkampudi: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Qiao Lin: Department of Environmental and Occupational Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, United States. ORCID
Saheli Mitra: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Aishwarya Vijai: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Weiheng Qin: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Ann Kang: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Jespar Chen: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Emma Ryan: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Runxuan Wang: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Yuqi Gong: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
Frank Heinrich: NIST Center for Neutron Research, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899, United States.
Junming Song: Department of Environmental and Occupational Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, United States.
Yuan-Pu Peter Di: Department of Environmental and Occupational Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, United States. ORCID
Stephanie Tristram-Nagle: Biological Physics, Physics Department, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States. ORCID
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(-)) bacteria , 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.
References
Biophys J. 2005 Apr;88(4):2626-37
[PMID: 15665131]
