Carmen Torres

Ismail Fliss

Laila Ben Said

Marc Ouellette

Phuong Nguyen-Phuong

Sofiane Telhig

Sylvie Rebuffat

Séverine Zirah

English

Repositorio de Universidad de La Rioja

  September 22-24 2022, The Royal Hotel, Hammamet, Tunisia                      THIRD INTERNATIONAL SYMPOSIUM ON NATURAL ANTIMICROBIALS:  Current status, challenges and perspectives  Book of abstracts  18  September 22-24 2022, The Royal Hotel, Hammamet, Tunisia THE POTENTIAL OF MICROCINS AS NEW THERAPIES. A PHENOTYPICAL AND GENOMIC STUDY OF THEIR EFFICIENCY REGARDING ENTEROBACTERIACEAE AND THEIR RESISTANCE MECHANISMS Sofiane Telhig1,2,3, Phuong Nguyen-Phuong4, Laila Ben Said1, Sylvie Rebuffat3, Carmen Torres5, Marc Ouellette4, Séverine Zirah3, Ismail Fliss1,2 1Food science department, Food and agriculture faculty, Laval University, Quebec, Quebec, Canada 2Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada 3Laboratoire Molécules de Communication et Adaptation des Microorganismes, Muséum National d’Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France 4Centre de recherche en Infectiologie et Axe des Maladies Infectieuses et Immunitaires du Centre de Recherche du CHU-Québec-Université Laval, 5Department of Food and Agriculture, University of La Rioja, Logroño, Spain Context: The emergence and spread of multi-resistant bacteria (MDRs) represents a major health risk. A notorious group of bacteria infamous for their capacity of evading and resisting antibiotics are Enterobacteriaceae. Microcins, antimicrobial peptides of enterobacteria produced ribosomally and targeting other Enterobacteriaceae, are a promising alternative to conventional antibiotics. Objectives: Study of microcin’s potential to inhibit MDR Enterobacteriaceae strains, as well as define their spectra of activity; explore possible synergistic/antagonistic effects; elucidate and characterize the mechanisms of resistance, co-resistance, and cross-resistance between microcins and antibiotics. Materials and Methods: The activity of four microcins: microcin J25 (a transcription-inhibiting lasso peptide), microcin C (a translation-inhibiting nucleotide peptide), microcin B17 (a modified microcin with thiazol oxazol rings) and microcin E492 (a siderophore peptide) was examined against a collection of 54 natural isolates, including several MDRs and covering a variety of serotypes distributed over three species: E. coli, K. pneumoniae and S. enterica. The ability of the four microcins to inhibit the collection of isolates was assessed by MIC and CMB measurements. Their potential synergistic/antagonistic effects were characterized by index FIC measures. The characterization of the resistance phenotypes observed against the tested microcins was conducted by comparison of the gene sequences involved in the mechanisms of action said microcins, as well as a non-targeted study GWAS (Genome Wide Association Study). Results and discussion: None of the strains tested were able to withstand all microcins at the concentrations tested (≤50 μ g/mL). Microcin C had the broadest inhibition spectrum, while microcin J25 had the most effective antimicrobial activities. Consortia microcins/antibiotics were the most beneficial. MFA analysis of microcin inhibition showed a single correlation between gentamicin resistance and MccJ25 resistance. In parallel, targeted, and non-targeted genomic analyses did not detect a correlation between antibiotic resistance patterns, virulence genes and microcin resistance. Resistance to each microcin was correlated with the presence of mutations in genes involved either in the import of microcin or in metabolism or stress response. Conclusions: Given the ability of the four microcins to inhibit varied Enterobacteriaceae species regardless of their antibiotic resistance gene and virulence genes arsenals. Our data highlights the potential of these microcins as new therapies. In addition, it is possible to overcome the narrow spectra of microcins by combining with each other or other antibiotics, since no antagonistic effects were recorded.

The potential of microcins as new therapies. A phenotypical and genomic study of their eficiency regarding enterobacteriaceae and their resistance mechamisms

https://investigacion.unirioja.es/documentos/646c620f7bb1586d2f053786/f/646c968c7bb1586d2f0537e4.pdf

The potential of microcins as new therapies. A phenotypical and genomic study of their eficiency regarding enterobacteriaceae and their resistance mechamisms

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