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

ABSTRACT: 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 Klebsiella 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.

SUBMITTER: Jakkampudi T

PROVIDER: S-EPMC10265666 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Jakkampudi Tanvi T Lin Qiao Q Mitra Saheli S Vijai Aishwarya A Qin Weiheng W Kang Ann A Chen Jespar J Ryan Emma E Wang Runxuan R Gong Yuqi Y Heinrich Frank F Song Junming J Di Yuan-Pu Peter YP Tristram-Nagle Stephanie S

Biomacromolecules 20230524 6

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 <i>Klebsiella pneumoniae</i>, obtained from 11 patients with/without colistin resistance. Secondary structural studies were carried out to study interactions betw ...[more]

PMID: 37223955

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Project description:Biofilms are surface-associated microbial communities known for their increased resistance to antimicrobials and host factors. This resistance introduces a critical clinical challenge, particularly in cases associated with implants increasing the predisposition for bacterial infections. Preventing such infections requires the development of novel antimicrobials or compounds that enhance bactericidal effect of currently available antibiotics. We have synthesized and characterized twelve novel silver(I) cyanoximates designated as Ag(ACO), Ag(BCO), Ag(CCO), Ag(ECO), Ag(PiCO), Ag(PICO) (yellow and red polymorphs), Ag(BIHCO), Ag(BIMCO), Ag(BOCO), Ag(BTCO), Ag(MCO) and Ag(PiPCO). The compounds exhibit a remarkable resistance to high intensity visible light, UV radiation and heat and have poor solubility in water. All these compounds can be well incorporated into the light-curable acrylate polymeric composites that are currently used as dental fillers or adhesives of indwelling medical devices. A range of dry weight % from 0.5 to 5.0 of the compounds was tested in this study. To study the potential of these compounds in preventing planktonic and biofilm growth of bacteria, we selected two human pathogens (Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus) and Gram-positive environmental isolate Bacillus aryabhattai. Both planktonic and biofilm growth was abolished completely in the presence of 0.5% to 5% of the compounds. The most efficient inhibition was shown by Ag(PiCO), Ag(BIHCO) and Ag(BTCO). The inhibition of biofilm growth by Ag(PiCO)-yellow was confirmed by scanning electron microscopy (SEM). Application of Ag(BTCO) and Ag(PiCO)-red in combination with tobramycin, the antibiotic commonly used to treat P. aeruginosa infections, showed a significant synergistic effect. Finally, the inhibitory effect lasted for at least 120 h in P. aeruginosa and 36 h in S. aureus and B. aryabhattai. Overall, several silver(I) cyanoximates complexes efficiently prevent biofilm development of both Gram-negative and Gram-positive bacteria and present a particularly significant potential for applications against P. aeruginosa infections.

Dataset Information

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

Publications

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

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