Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae

Levi A. C. Branco
,
Pedro Filho Noronha Souza
* ORCID logo ,
Nilton A. S. Neto
,
Tawanny K. B. Aguiar
ORCID logo ,
Ayrles F. B. Silva
,
Rômulo F Carneiro
,
Celso S Nagano
,
Felipe Pantoja Mesquita
,
Luina Benevides Lima
,
Cleverson D. T. Freitas
ORCID logo
Version 1 : Received: 15 November 2022 / Approved: 16 November 2022 / Online: 16 November 2022 (13:15:11 CET)

A peer-reviewed article of this Preprint also exists.

Branco, L.A.C.; Souza, P.F.N.; Neto, N.A.S.; Aguiar, T.K.B.; Silva, A.F.B.; Carneiro, R.F.; Nagano, C.S.; Mesquita, F.P.; Lima, L.B.; Freitas, C.D.T. New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae. Antibiotics 2022, 11, 1753. Branco, L.A.C.; Souza, P.F.N.; Neto, N.A.S.; Aguiar, T.K.B.; Silva, A.F.B.; Carneiro, R.F.; Nagano, C.S.; Mesquita, F.P.; Lima, L.B.; Freitas, C.D.T. New Insights into the Mechanism of Antibacterial Action of Synthetic Peptide Mo-CBP3-PepI against Klebsiella pneumoniae. Antibiotics 2022, 11, 1753.

Abstract

Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, it was seen a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics. These reductions lead to the inhibition of DNA repair, inhibition of cell wall turnover, protein turnover, and ROS accumulation leading to cell death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

Keywords

Antimicrobial peptides; Synthetic peptides; multidrug resistant bacteria; proteomic analysis

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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