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A Novel Cryptic Clostridial Peptide That Kills Bacteria by a Cell Membrane Permeabilization Mechanism

Abstract

This work reports detailed characteristics of the antimicrobial peptide Intestinalin (P30), which is derived from the LysC enzyme of Clostridium intestinale strain URNW. The peptide shows a broader antibacterial spectrum than the parental enzyme, showing potent antimicrobial activity against clinical strains of Gram-positive staphylococci and Gram-negative pathogens and causing between 3.04 ± 0.12 log kill for Pseudomonas aeruginosa PAO1 and 7.10 ± 0.05 log kill for multidrug-resistant Acinetobacter baumannii KPD 581 at a 5 μM concentration. Moreover, Intestinalin (P30) prevents biofilm formation and destroys 24-h and 72-h biofilms formed by Acinetobacter baumannii CRAB KPD 205 (reduction levels of 4.28 and 2.62 log CFU/mL, respectively). The activity of Intestinalin is combined with both no cytotoxicity and little hemolytic effect against mammalian cells. The nuclear magnetic resonance and molecular dynamics (MD) data show a high tendency of Intestinalin to interact with the bacterial phospholipid cell membrane. Although positively charged, Intestinalin resides in the membrane and aggregates into small oligomers. Negatively charged phospholipids stabilize peptide oligomers to form water- and ion-permeable pores, disrupting the integrity of bacterial cell membranes. Experimental data showed that Intestinalin interacts with negatively charged lipoteichoic acid (logK based on isothermal titration calorimetry, 7.45 ± 0.44), causes membrane depolarization, and affects membrane integrity by forming large pores, all of which result in loss of bacterial viability.

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Authors (15)

Keywords

Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
Microbiology Spectrum no. 10,
ISSN:
Language:
English
Publication year:
2022
Bibliographic description:
Szadkowska M., Olewniczak M., Kloska A., Jankowska E., Kapusta M., Rybak B., Wyrzykowski D., Zmudzinska W., Gieldon A., Kocot A., Kaczorowska A., Nierzwicki Ł., Makowska J., Kaczorowski T., Płotka M.: A Novel Cryptic Clostridial Peptide That Kills Bacteria by a Cell Membrane Permeabilization Mechanism// Microbiology Spectrum -Vol. 10,iss. 5 (2022),
DOI:
Digital Object Identifier (open in new tab) 10.1128/spectrum.01657-22
Sources of funding:
  • COST_FREE
Verified by:
Gdańsk University of Technology

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