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The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids

Free fatty acids (FFAs) are known to exhibit antimicrobial and anti-virulent properties against bacterial pathogens. Specific FFAs, such as lauric acid (LA; C12:0), exert both effects against the foodborne pathogen Listeria monocytogenes: at low levels, LA acts to inhibit the activity of the virulen...

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Autores principales: Thomasen, Rikke S. S., Jespersen, Magnus Ganer, Jørgensen, Katrine, dos Santos, Patricia T., Sternkopf Lillebæk, Eva M., Skov, Marianne N., Kemp, Michael, Kallipolitis, Birgitte H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113694/
https://www.ncbi.nlm.nih.gov/pubmed/35591996
http://dx.doi.org/10.3389/fmicb.2022.895942
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author Thomasen, Rikke S. S.
Jespersen, Magnus Ganer
Jørgensen, Katrine
dos Santos, Patricia T.
Sternkopf Lillebæk, Eva M.
Skov, Marianne N.
Kemp, Michael
Kallipolitis, Birgitte H.
author_facet Thomasen, Rikke S. S.
Jespersen, Magnus Ganer
Jørgensen, Katrine
dos Santos, Patricia T.
Sternkopf Lillebæk, Eva M.
Skov, Marianne N.
Kemp, Michael
Kallipolitis, Birgitte H.
author_sort Thomasen, Rikke S. S.
collection PubMed
description Free fatty acids (FFAs) are known to exhibit antimicrobial and anti-virulent properties against bacterial pathogens. Specific FFAs, such as lauric acid (LA; C12:0), exert both effects against the foodborne pathogen Listeria monocytogenes: at low levels, LA acts to inhibit the activity of the virulence regulator PrfA, whereas at higher levels, LA inhibits bacterial growth. Deletion of prfA is known to promote tolerance toward antimicrobial FFAs, suggesting that the response of L. monocytogenes to anti-virulent and antimicrobial FFAs could be linked. In this study, we explored the response of L. monocytogenes toward antimicrobial FFAs holding an anti-virulence activity by isolating strains that can grow at high concentrations of LA. We found that LA-tolerant isolates carry mutations in the gene encoding the global regulator CcpA. Importantly, we discovered that mutation or deletion of ccpA protect L. monocytogenes against the antimicrobial activity of FFAs, whereas the ccpA mutants remain sensitive toward FFA’s PrfA inhibitory effect. A regulatory link involving CcpA, connecting the response toward the antimicrobial and anti-virulence activities of FFAs, is therefore unlikely. To further study how deletion of ccpA promotes FFA tolerance, we performed a transcriptomic analysis of the response to LA. Our data indicated that the FFA-tolerant phenotype of the ∆ccpA strain is not induced upon LA exposure but appears to be an inherent phenotypic trait of the ccpA deletion mutation. Interestingly, we found that the bacterial surface of L. monocytogenes becomes more hydrophilic upon deletion of ccpA, and we demonstrate that CcpA plays a role in the response of L. monocytogenes to other stress conditions, including low pH and antibiotics. Altogether, our study revealed that regulatory activities of CcpA lead to an increased hydrophobicity of the bacterial surface, which may confer sensitivity of L. monocytogenes against the antimicrobial activity of FFAs. Notably, CcpA is not involved in responding to the PrfA inhibitory effect of FFAs, showing that FFA-tolerant strains can still be targeted by the anti-virulent activity of FFAs.
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spelling pubmed-91136942022-05-18 The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids Thomasen, Rikke S. S. Jespersen, Magnus Ganer Jørgensen, Katrine dos Santos, Patricia T. Sternkopf Lillebæk, Eva M. Skov, Marianne N. Kemp, Michael Kallipolitis, Birgitte H. Front Microbiol Microbiology Free fatty acids (FFAs) are known to exhibit antimicrobial and anti-virulent properties against bacterial pathogens. Specific FFAs, such as lauric acid (LA; C12:0), exert both effects against the foodborne pathogen Listeria monocytogenes: at low levels, LA acts to inhibit the activity of the virulence regulator PrfA, whereas at higher levels, LA inhibits bacterial growth. Deletion of prfA is known to promote tolerance toward antimicrobial FFAs, suggesting that the response of L. monocytogenes to anti-virulent and antimicrobial FFAs could be linked. In this study, we explored the response of L. monocytogenes toward antimicrobial FFAs holding an anti-virulence activity by isolating strains that can grow at high concentrations of LA. We found that LA-tolerant isolates carry mutations in the gene encoding the global regulator CcpA. Importantly, we discovered that mutation or deletion of ccpA protect L. monocytogenes against the antimicrobial activity of FFAs, whereas the ccpA mutants remain sensitive toward FFA’s PrfA inhibitory effect. A regulatory link involving CcpA, connecting the response toward the antimicrobial and anti-virulence activities of FFAs, is therefore unlikely. To further study how deletion of ccpA promotes FFA tolerance, we performed a transcriptomic analysis of the response to LA. Our data indicated that the FFA-tolerant phenotype of the ∆ccpA strain is not induced upon LA exposure but appears to be an inherent phenotypic trait of the ccpA deletion mutation. Interestingly, we found that the bacterial surface of L. monocytogenes becomes more hydrophilic upon deletion of ccpA, and we demonstrate that CcpA plays a role in the response of L. monocytogenes to other stress conditions, including low pH and antibiotics. Altogether, our study revealed that regulatory activities of CcpA lead to an increased hydrophobicity of the bacterial surface, which may confer sensitivity of L. monocytogenes against the antimicrobial activity of FFAs. Notably, CcpA is not involved in responding to the PrfA inhibitory effect of FFAs, showing that FFA-tolerant strains can still be targeted by the anti-virulent activity of FFAs. Frontiers Media S.A. 2022-05-03 /pmc/articles/PMC9113694/ /pubmed/35591996 http://dx.doi.org/10.3389/fmicb.2022.895942 Text en Copyright © 2022 Thomasen, Jespersen, Jørgensen, dos Santos, Sternkopf Lillebæk, Skov, Kemp and Kallipolitis. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Thomasen, Rikke S. S.
Jespersen, Magnus Ganer
Jørgensen, Katrine
dos Santos, Patricia T.
Sternkopf Lillebæk, Eva M.
Skov, Marianne N.
Kemp, Michael
Kallipolitis, Birgitte H.
The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title_full The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title_fullStr The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title_full_unstemmed The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title_short The Global Regulator CcpA of Listeria monocytogenes Confers Sensitivity to Antimicrobial Fatty Acids
title_sort global regulator ccpa of listeria monocytogenes confers sensitivity to antimicrobial fatty acids
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113694/
https://www.ncbi.nlm.nih.gov/pubmed/35591996
http://dx.doi.org/10.3389/fmicb.2022.895942
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