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Peer-reviewedCC BY 4.0BMC Microbiology

Microbiological and genomic approaches to study and characterize co- and cross-resistance to antimicrobial peptides in Listeria monocytogenes ATCC 19,111 variants

  • Omar Fliss1,2,3,4
  • Louis-David Guay2,3,4,5
  • Nguyen Phuong Pham2,3,6
  • Philippe Leprohon2,3,6
  • Ramzi Guerbaa1,4
  • Marc Ouellette2,3,6
  • Natalie Fava7
  • Franco Pagotto7
  • Éric Biron2,3,4,5
  • Ismail Fliss1,3,4
7 affiliations
  1. 1Département des Sciences des Aliments, Faculté des Sciences de l’agriculture et de l’alimentation, Université Laval, Québec (QC), Canada
  2. 2Centre de Recherche du CHU de Québec-Université Laval, Québec (QC), Canada
  3. 3Research Center in Infectious Diseases, Université Laval, Québec (QC), Canada
  4. 4Institut of Nutrition and Functional Foods, Université Laval, Québec (QC), Canada
  5. 5Faculté de Pharmacie, The Quebec Network for Research on Protein Function, Engineering, and Applications, Université Laval and PROTEO, Québec (QC), Canada
  6. 6Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université Laval, Québec (QC), Canada
  7. 7Listeriosis Reference Centre, Food Safety Regulatory Research Division, Bureau of Microbial and Toxicological Food Safety, Food and Nutrition Directorate, Health Canada, Ottawa, Canada
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Abstract

Background: Antimicrobial peptides are considered a promising alternative to conventional antibiotics for controlling Listeria monocytogenes, a major foodborne pathogen. However, the emergence of antimicrobial resistance, including co- and cross-resistance between structurally and functionally distinct peptides, remains a critical and insufficiently explored challenge. This study aimed to investigate and characterize the mechanisms underlying co- and cross-resistance among five distinct antimicrobial peptides: nisin Z, pediocin PA-1, plantaricin S, brevibacillin, and its synthetic analog brevibacillin Thr1, selected for their diverse structures and modes of action.

Results: All tested peptides exhibited strong anti-listerial activity, with minimum inhibitory concentrations ranging from 0.5 to 15 µM and minimum bactericidal concentrations from 1 to 60 µM. Resistant variants were generated through stepwise adaptive evolution by exposing Listeria monocytogenes ATCC 19,111 to gradually increasing peptide concentrations. These variants were characterized based on resistance levels, growth rates, and resistance stability. No cross-resistance was observed between antimicrobial peptides and conventional antibiotics. However, co-resistance and cross-resistance were identified among certain peptides, particularly those sharing structural or functional similarities, suggesting overlapping or convergent resistance mechanisms. Whole-genome sequencing and metabolic analyses revealed distinct genetic mutations associated with resistance phenotypes, along with specific alterations in metabolic pathways.

Conclusion: This study demonstrates that Listeria monocytogenes ATCC 19,111 can develop co- and cross-resistance to antimicrobial peptides, especially among structurally or functionally related compounds. The findings highlight the complexity of resistance mechanisms and emphasize the importance of integrating genomic and metabolic approaches to better understand adaptive responses to antimicrobial pressure. These insights may inform the development of more effective antimicrobial strategies and support the rational design of peptide-based interventions to control foodborne pathogens.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12866-026-05467-w.

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Cite

BibTeXRIS
BibTeX
@article{fliss2026microbiological,
  title = {{Microbiological and genomic approaches to study and characterize co- and cross-resistance to antimicrobial peptides in Listeria monocytogenes ATCC 19,111 variants}},
  author = {Omar Fliss and Louis-David Guay and Nguyen Phuong Pham and Philippe Leprohon and Ramzi Guerbaa and Marc Ouellette and Natalie Fava and Franco Pagotto and Éric Biron and Ismail Fliss},
  journal = {BMC Microbiology},
  year = {2026},
  month = aug,
  doi = {10.1186/s12866-026-05467-w},
  url = {https://doi.org/10.1186/s12866-026-05467-w},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Microbiological and genomic approaches to study and characterize co- and cross-resistance to antimicrobial peptides in Listeria monocytogenes ATCC 19,111 variants
AU  - Omar Fliss
AU  - Louis-David Guay
AU  - Nguyen Phuong Pham
AU  - Philippe Leprohon
AU  - Ramzi Guerbaa
AU  - Marc Ouellette
AU  - Natalie Fava
AU  - Franco Pagotto
AU  - Éric Biron
AU  - Ismail Fliss
PY  - 2026
DA  - 2026/08/07
JO  - BMC Microbiology
DO  - 10.1186/s12866-026-05467-w
UR  - https://doi.org/10.1186/s12866-026-05467-w
AB  - Background: Antimicrobial peptides are considered a promising alternative to conventional antibiotics for controlling Listeria monocytogenes, a major foodborne pathogen. However, the emergence of antimicrobial resistance, including co- and cross-resistance between structurally and functionally distinct peptides, remains a critical and insufficiently explored challenge. This study aimed to investigate and characterize the mechanisms underlying co- and cross-resistance among five distinct antimicrobial peptides: nisin Z, pediocin PA-1, plantaricin S, brevibacillin, and its synthetic analog brevibacillin Thr1, selected for their diverse structures and modes of action.  Results: All tested peptides exhibited strong anti-listerial activity, with minimum inhibitory concentrations ranging from 0.5 to 15 µM and minimum bactericidal concentrations from 1 to 60 µM. Resistant variants were generated through stepwise adaptive evolution by exposing Listeria monocytogenes ATCC 19,111 to gradually increasing peptide concentrations. These variants were characterized based on resistance levels, growth rates, and resistance stability. No cross-resistance was observed between antimicrobial peptides and conventional antibiotics. However, co-resistance and cross-resistance were identified among certain peptides, particularly those sharing structural or functional similarities, suggesting overlapping or convergent resistance mechanisms. Whole-genome sequencing and metabolic analyses revealed distinct genetic mutations associated with resistance phenotypes, along with specific alterations in metabolic pathways.  Conclusion: This study demonstrates that Listeria monocytogenes ATCC 19,111 can develop co- and cross-resistance to antimicrobial peptides, especially among structurally or functionally related compounds. The findings highlight the complexity of resistance mechanisms and emphasize the importance of integrating genomic and metabolic approaches to better understand adaptive responses to antimicrobial pressure. These insights may inform the development of more effective antimicrobial strategies and support the rational design of peptide-based interventions to control foodborne pathogens.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12866-026-05467-w.
SN  - 1471-2180
ER  -