Microscopic and metabolomics analysis of the anti-Listeria activity of natural and engineered cruzioseptins.

Autor: Bermúdez-Puga S; Microbial Biomolecules Laboratory, Faculty of Pharmaceutical Sciences, University of São Paulo, Rua do Lago 250, São Paulo, 05508-000, SP, Brazil., Dias M; Dempster MS Lab, Chemical Engineering Department of Polytechnic School of University of São Paulo, Rua do Lago 250, São Paulo, 05508-080, SP, Brazil., Lima Reis I; Microbial Biomolecules Laboratory, Faculty of Pharmaceutical Sciences, University of São Paulo, Rua do Lago 250, São Paulo, 05508-000, SP, Brazil., Freire de Oliveira T; Microbial Biomolecules Laboratory, Faculty of Pharmaceutical Sciences, University of São Paulo, Rua do Lago 250, São Paulo, 05508-000, SP, Brazil., Yokomizo de Almeida SR; Department of Anatomy, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil., Mendes MA; Dempster MS Lab, Chemical Engineering Department of Polytechnic School of University of São Paulo, Rua do Lago 250, São Paulo, 05508-080, SP, Brazil., Moore SJ; School of Biological and Behavioural Sciences, Queen Mary University of London, UK., Almeida JR; Biomolecules Discovery Group, Universidad Regional Amazónica Ikiam, Km 7 Via Muyuna, Tena, Napo, Ecuador; School of Pharmacy, University of Reading, Reading, RG6 6UB, UK., Proaño-Bolaños C; Biomolecules Discovery Group, Universidad Regional Amazónica Ikiam, Km 7 Via Muyuna, Tena, Napo, Ecuador., Pinheiro de Souza Oliveira R; Microbial Biomolecules Laboratory, Faculty of Pharmaceutical Sciences, University of São Paulo, Rua do Lago 250, São Paulo, 05508-000, SP, Brazil. Electronic address: rpsolive@usp.br.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2024 Oct; Vol. 225, pp. 168-175. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.biochi.2024.05.022
Abstrakt: Listeria monocytogenes is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the in vitro anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the in vitro potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 μM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-Listeria bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is not resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of L. monocytogenes emergence and dissemination.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
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Databáze: MEDLINE