Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections impact all patient populations both in the community and in health care settings. Despite advances in our knowledge of MRSA virulence, little is known about the regulatory mechanisms of USA100 health care-associated MRSA isolates...

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Autores principales:	Morgan L. Grundstad, Corey P. Parlet, Jakub M. Kwiecinski, Jeffrey S. Kavanaugh, Heidi A. Crosby, Young-Saeng Cho, Kristopher Heilmann, Daniel J. Diekema, Alexander R. Horswill
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	MRSA USA100 agr quorum sensing Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0a24134852d24219b10c590d69fc61ab
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spelling	oai:doaj.org-article:0a24134852d24219b10c590d69fc61ab2021-11-15T15:22:26ZQuorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates10.1128/mSphere.00553-192379-5042https://doaj.org/article/0a24134852d24219b10c590d69fc61ab2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00553-19https://doaj.org/toc/2379-5042ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections impact all patient populations both in the community and in health care settings. Despite advances in our knowledge of MRSA virulence, little is known about the regulatory mechanisms of USA100 health care-associated MRSA isolates, which are the second most frequently identified MRSA isolates found in all infections. This work focused on the contribution of the USA100 agr type II quorum-sensing system to virulence and antibiotic resistance. From a MRSA strain collection, we selected 16 representative USA100 isolates, constructed mutants with Δagr mutations, and characterized selected strain pairs for virulence factor expression, murine skin infection, and antibiotic resistance. For each strain pair, hemolysis and extracellular protease expression were significantly greater in the wild-type (WT) strains than in the Δagr mutants. Similarly, mice challenged with the WT strains had larger areas of dermonecrosis and greater weight loss than those challenged with the Δagr mutants, demonstrating that the USA100 agr system regulates virulence. Although USA100 isolates exhibit a high level of antibiotic resistance, the WT and Δagr strain pairs showed no difference in MICs by MIC testing. However, in the presence of a sub-MIC of vancomycin, most of the USA100 Δagr mutants exhibited slower growth than the WT isolates, and a couple of the Δagr mutants also grew more slowly in the presence of a sub-MIC of cefoxitin. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence, and it may have a contribution to the optimal survival of these MRSA strains in the presence of antibiotics. IMPORTANCE USA100 health care-associated MRSA isolates are highly antibiotic resistant and can cause invasive disease across all patient populations. Even though USA100 strains are some of the most frequently identified causes of infections, little is known about virulence regulation in these isolates. Our study demonstrates that the USA100 agr quorum-sensing system is important for the control of toxin and exoenzyme production and that the agr system has a key role in skin infection. In some USA100 isolates, the agr system is important for growth in the presence of low levels of antibiotics. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence and that it may make a contribution to the optimal survival of these MRSA strains in the presence of antibiotics.Morgan L. GrundstadCorey P. ParletJakub M. KwiecinskiJeffrey S. KavanaughHeidi A. CrosbyYoung-Saeng ChoKristopher HeilmannDaniel J. DiekemaAlexander R. HorswillAmerican Society for MicrobiologyarticleMRSAUSA100agrquorum sensingMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	MRSA USA100 agr quorum sensing Microbiology QR1-502
spellingShingle	MRSA USA100 agr quorum sensing Microbiology QR1-502 Morgan L. Grundstad Corey P. Parlet Jakub M. Kwiecinski Jeffrey S. Kavanaugh Heidi A. Crosby Young-Saeng Cho Kristopher Heilmann Daniel J. Diekema Alexander R. Horswill Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
description	ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections impact all patient populations both in the community and in health care settings. Despite advances in our knowledge of MRSA virulence, little is known about the regulatory mechanisms of USA100 health care-associated MRSA isolates, which are the second most frequently identified MRSA isolates found in all infections. This work focused on the contribution of the USA100 agr type II quorum-sensing system to virulence and antibiotic resistance. From a MRSA strain collection, we selected 16 representative USA100 isolates, constructed mutants with Δagr mutations, and characterized selected strain pairs for virulence factor expression, murine skin infection, and antibiotic resistance. For each strain pair, hemolysis and extracellular protease expression were significantly greater in the wild-type (WT) strains than in the Δagr mutants. Similarly, mice challenged with the WT strains had larger areas of dermonecrosis and greater weight loss than those challenged with the Δagr mutants, demonstrating that the USA100 agr system regulates virulence. Although USA100 isolates exhibit a high level of antibiotic resistance, the WT and Δagr strain pairs showed no difference in MICs by MIC testing. However, in the presence of a sub-MIC of vancomycin, most of the USA100 Δagr mutants exhibited slower growth than the WT isolates, and a couple of the Δagr mutants also grew more slowly in the presence of a sub-MIC of cefoxitin. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence, and it may have a contribution to the optimal survival of these MRSA strains in the presence of antibiotics. IMPORTANCE USA100 health care-associated MRSA isolates are highly antibiotic resistant and can cause invasive disease across all patient populations. Even though USA100 strains are some of the most frequently identified causes of infections, little is known about virulence regulation in these isolates. Our study demonstrates that the USA100 agr quorum-sensing system is important for the control of toxin and exoenzyme production and that the agr system has a key role in skin infection. In some USA100 isolates, the agr system is important for growth in the presence of low levels of antibiotics. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence and that it may make a contribution to the optimal survival of these MRSA strains in the presence of antibiotics.
format	article
author	Morgan L. Grundstad Corey P. Parlet Jakub M. Kwiecinski Jeffrey S. Kavanaugh Heidi A. Crosby Young-Saeng Cho Kristopher Heilmann Daniel J. Diekema Alexander R. Horswill
author_facet	Morgan L. Grundstad Corey P. Parlet Jakub M. Kwiecinski Jeffrey S. Kavanaugh Heidi A. Crosby Young-Saeng Cho Kristopher Heilmann Daniel J. Diekema Alexander R. Horswill
author_sort	Morgan L. Grundstad
title	Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
title_short	Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
title_full	Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
title_fullStr	Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
title_full_unstemmed	Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates
title_sort	quorum sensing, virulence, and antibiotic resistance of usa100 methicillin-resistant <named-content content-type="genus-species">staphylococcus aureus</named-content> isolates
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/0a24134852d24219b10c590d69fc61ab
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Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Isolates

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