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Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance

Bacteria can adapt to a changing environment by adopting alternate metabolic states favoring small molecule synthesis and resilience over growth. In Staphylococcus aureus, these states are induced by factors present during infection, including nutritional limitations, host responses and competition...

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Autores principales: Meredith, Emily M., Harven, Lauren T., Berti, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774428/
https://www.ncbi.nlm.nih.gov/pubmed/36551467
http://dx.doi.org/10.3390/antibiotics11121810
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author Meredith, Emily M.
Harven, Lauren T.
Berti, Andrew D.
author_facet Meredith, Emily M.
Harven, Lauren T.
Berti, Andrew D.
author_sort Meredith, Emily M.
collection PubMed
description Bacteria can adapt to a changing environment by adopting alternate metabolic states favoring small molecule synthesis and resilience over growth. In Staphylococcus aureus, these states are induced by factors present during infection, including nutritional limitations, host responses and competition with other bacteria. Isogenic “tolerant” populations have variable responses to antibiotics and can remain viable. In this study, we compared the capability of antibiotics to reduce the viability of S. aureus made tolerant by different mechanisms. Tolerance was induced with mupirocin, HQNO, peroxynitrite or human serum. Tolerant cultures were exposed to ceftaroline, daptomycin, gentamicin, levofloxacin, oritavancin or vancomycin at physiological concentrations, and the viability was assessed by dilution plating. The minimum duration for 3-log viability reduction and 24 h viability reduction were calculated independently for each of three biological replicates. Each tolerance mechanism rendered at least one antibiotic ineffective, and each antibiotic was rendered ineffective by at least one mechanism of tolerance. Further studies to evaluate additional antibiotics, combination therapy and different tolerance inducers are warranted.
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spelling pubmed-97744282022-12-23 Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance Meredith, Emily M. Harven, Lauren T. Berti, Andrew D. Antibiotics (Basel) Article Bacteria can adapt to a changing environment by adopting alternate metabolic states favoring small molecule synthesis and resilience over growth. In Staphylococcus aureus, these states are induced by factors present during infection, including nutritional limitations, host responses and competition with other bacteria. Isogenic “tolerant” populations have variable responses to antibiotics and can remain viable. In this study, we compared the capability of antibiotics to reduce the viability of S. aureus made tolerant by different mechanisms. Tolerance was induced with mupirocin, HQNO, peroxynitrite or human serum. Tolerant cultures were exposed to ceftaroline, daptomycin, gentamicin, levofloxacin, oritavancin or vancomycin at physiological concentrations, and the viability was assessed by dilution plating. The minimum duration for 3-log viability reduction and 24 h viability reduction were calculated independently for each of three biological replicates. Each tolerance mechanism rendered at least one antibiotic ineffective, and each antibiotic was rendered ineffective by at least one mechanism of tolerance. Further studies to evaluate additional antibiotics, combination therapy and different tolerance inducers are warranted. MDPI 2022-12-13 /pmc/articles/PMC9774428/ /pubmed/36551467 http://dx.doi.org/10.3390/antibiotics11121810 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Meredith, Emily M.
Harven, Lauren T.
Berti, Andrew D.
Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title_full Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title_fullStr Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title_full_unstemmed Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title_short Antimicrobial Efficacy against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
title_sort antimicrobial efficacy against antibiotic-tolerant staphylococcus aureus depends on the mechanism of antibiotic tolerance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774428/
https://www.ncbi.nlm.nih.gov/pubmed/36551467
http://dx.doi.org/10.3390/antibiotics11121810
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