Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant Staphylococcus aureus Isolates

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

doi:10.1128/msphere.00553-19

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Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant Staphylococcus aureus Isolates

Journal article

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Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant Staphylococcus aureus Isolates

Morgan L Grundstad, Corey P Parlet, Jakub M Kwiecinski, Jeffrey S Kavanaugh, Heidi A Crosby, Young-Saeng Cho, Kristopher Heilmann, Daniel J Diekema and Alexander R Horswill

mSphere, Vol.4(4)

08/14/2019

DOI: 10.1128/msphere.00553-19

PMCID: PMC6695519

PMID: 31413175

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Abstract

Methicillin-resistant (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 type II quorum-sensing system to virulence and antibiotic resistance. From a MRSA strain collection, we selected 16 representative USA100 isolates, constructed mutants with Δ 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 Δ mutants. Similarly, mice challenged with the WT strains had larger areas of dermonecrosis and greater weight loss than those challenged with the Δ mutants, demonstrating that the USA100 system regulates virulence. Although USA100 isolates exhibit a high level of antibiotic resistance, the WT and Δ strain pairs showed no difference in MICs by MIC testing. However, in the presence of a sub-MIC of vancomycin, most of the USA100 Δ mutants exhibited slower growth than the WT isolates, and a couple of the Δ mutants also grew more slowly in the presence of a sub-MIC of cefoxitin. Altogether, our findings demonstrate that the USA100 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. 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 quorum-sensing system is important for the control of toxin and exoenzyme production and that the system has a key role in skin infection. In some USA100 isolates, the system is important for growth in the presence of low levels of antibiotics. Altogether, our findings demonstrate that the USA100 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.

Quorum Sensing

Virulence Factors - genetics

Humans

Methicillin-Resistant Staphylococcus aureus - drug effects

Virulence

Bacterial Proteins - genetics

Microbial Sensitivity Tests

Methicillin-Resistant Staphylococcus aureus - pathogenicity

Animals

Drug Resistance, Multiple, Bacterial

Trans-Activators - genetics

Anti-Bacterial Agents - pharmacology

Mice

Mice, Inbred BALB C

Staphylococcal Infections - microbiology

Methicillin-Resistant Staphylococcus aureus - genetics

Details

Title: Subtitle: Quorum Sensing, Virulence, and Antibiotic Resistance of USA100 Methicillin-Resistant Staphylococcus aureus Isolates
Creators: Morgan L Grundstad - University of Iowa Stead Family Children's Hospital, Iowa City, Iowa, USA
Corey P Parlet - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Jakub M Kwiecinski - Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Jeffrey S Kavanaugh - Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Heidi A Crosby - Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Young-Saeng Cho - Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
Kristopher Heilmann - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Daniel J Diekema - Division of Medical Microbiology, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Alexander R Horswill - Department of Veterans Affairs Eastern Colorado Healthcare System, Aurora, Colorado, USA
Resource Type: Journal article
Publication Details: mSphere, Vol.4(4)
DOI: 10.1128/msphere.00553-19
PMID: 31413175
PMCID: PMC6695519
NLM abbreviation: mSphere
ISSN: 2379-5042
eISSN: 2379-5042
Publisher: United States
Grant note: I01 BX002711 / BLRD VA P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 08/14/2019
Academic Unit: Microbiology and Immunology; Infectious Diseases; Pathology; Internal Medicine
Record Identifier: 9984001235802771

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