Dual antibacterial mechanism of [K4K15]CZS-1 against Salmonella Typhimurium: a membrane active and intracellular-targeting antimicrobial peptide

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Bermudez-Puga, Sebastian ; Dias, Meriellen ; de Oliveira, Taciana Freire ; Mendonca, Carlos Miguel Nobrega ; de Almeida, Sonia Regina Yokomizo ; Rozas, Enrique Eduardo ; do Nascimento, Claudio Augusto Oller ; Mendes, Maria Anita ; de Azevedo, Pamela Oliveira De Souza ; Almeida, Jose R. ; Proano-Bolanos, Carolina ; Oliveira, Ricardo Pinheiro de Souza

• Document type: Journal article
• Source: FRONTIERS IN MICROBIOLOGY; v. 14, p. 14-pg., 2023-12-14.

Abstract

Salmonella genus is a leading cause of food-borne infections with strong public health impact and economic ramifications. The development of antimicrobial resistance added complexity to this scenario and turned the antibiotic drug discovery into a highly important challenge. The screening of peptides has served as a successful discovery platform to design new antibiotic candidates. Motivated by this, the antimicrobial and cytotoxic properties of three cruzioseptins against Salmonella Typhimurium and RAW 264.7 murine macrophage cells, respectively, were investigated. [K4K15]CZS-1 was the most potent antimicrobial peptide identified in the screening step with a minimum inhibitory concentration (MIC) of 16 mu g/mL (7.26 mu M) and moderate cytotoxicity. From a structural point of view, in vitro and in silico techniques evidenced that [K4K15]CZS-1 is a alpha-helical cationic antimicrobial peptide. In order to capture mechanistic details and fully decipher their antibacterial action, we adopted a multidimensional approach, including spectroscopy, electron microscopy and omics analysis. In general lines, [K4K15]CZS-1 caused membrane damage, intracellular alterations in Salmonella and modulated metabolic pathways, such as the tricarboxylic acid (TCA) cycle, fatty acid biosynthesis, and lipid metabolism. Overall, these findings provide deeper insights into the antibacterial properties and multidimensional mode of action of [K4K15]CZS-1 against Salmonella Typhimurium. In summary, this study represents a first step toward the screening of membrane-acting and intracellular-targeting peptides as potential bio-preservatives to prevent foodborne outbreaks caused by Salmonella. (AU)

• FAPESP's process: 22/07556-3 - Bioprospecting of probiotic bacteria producing bacteriocins and vitamins: from culture optimization to the application in poultry production system
• Grantee: Pamela Oliveira de Souza de Azevedo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15599-9 - Mult-user Equipment approved in grant 2018/25511-1: Semi-Preparative High Pressure Liquid Chromatography
• Grantee: Ricardo Pinheiro de Souza Oliveira
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/04841-9 - Selection and identification of bacteriocin-producing probiotic strains
• Grantee: Meriellen Dias Pantolfi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/25511-1 - Bioprospecting of bacteriocin-producing bacteria: from culture optimization to the application in animal production systems
• Grantee: Ricardo Pinheiro de Souza Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/02936-2 - Probiotics and bacteriocins in Nile Tilapia feeding: effects on growth performance, immunology and experimental infection
• Grantee: Sebastián Armando Bermúdez Puga
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)