Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria

被引：6

作者：

Jakkampudi, Tanvi ^{[1
]}

Lin, Qiao ^{[2
]}

Mitra, Saheli ^{[1
]}

Vijai, Aishwarya ^{[1
]}

Qin, Weiheng ^{[1
]}

Kang, Ann ^{[1
]}

Chen, Jespar ^{[1
]}

Ryan, Emma ^{[1
]}

Wang, Runxuan ^{[1
]}

Gong, Yuqi ^{[1
]}

Heinrich, Frank ^{[3
]}

Song, Junming ^{[2
]}

Di, Yuan-Pu ^{[2
]}

Tristram-Nagle, Stephanie ^{[1
]}

机构：

[1] Carnegie Mellon Univ, Phys Dept, Biol Phys, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15261 USA

[3] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA

来源：

BIOMACROMOLECULES | 2023年 / 24卷 / 06期

基金：

美国安德鲁·梅隆基金会; 美国国家卫生研究院; 美国国家科学基金会;

关键词：

X-RAY-SCATTERING; ANTIMICROBIAL PEPTIDES; HELICITY; COLISTIN; NEUTRON; MECHANISMS; BILAYERS;

D O I：

10.1021/acs.biomac.3c00218

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SPLUNC1 (short palate lung and nasal epithelial clone 1) is a multifunctionalhost defense protein found in human respiratory tract with antimicrobialproperties. In this work, we compare the biological activities offour SPLUNC1 antimicrobial peptide (AMP) derivatives using pairedclinical isolates of the Gram-negative (G(-)) bacteria Klebsiella pneumoniae, obtained from 11 patientswith/without colistin resistance. Secondary structural studies werecarried out to study interactions between the AMPs and lipid modelmembranes (LMMs) utilizing circular dichroism (CD). Two peptides werefurther characterized using X-ray diffuse scattering (XDS) and neutronreflectivity (NR). A4-153 displayed superior antibacterial activityin both G(-) planktonic cultures and biofilms. NR and XDS revealedthat 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 helicalcharacter, demonstrating that helicity and efficacy are correlatedin these SPLUNC1 AMPs.

引用

页码：2804 / 2815

页数：12

共 44 条

[1] Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer Composition and Protein Lipidation [J].