Cargando…
Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerston...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539228/ https://www.ncbi.nlm.nih.gov/pubmed/34683376 http://dx.doi.org/10.3390/microorganisms9102055 |
_version_ | 1784588695988338688 |
---|---|
author | Kumaraswamy, Monika Wiull, Kamilla Joshi, Bishnu Sakoulas, George Kousha, Armin Vaaje-Kolstad, Gustav Johannessen, Mona Hegstad, Kristin Nizet, Victor Askarian, Fatemeh |
author_facet | Kumaraswamy, Monika Wiull, Kamilla Joshi, Bishnu Sakoulas, George Kousha, Armin Vaaje-Kolstad, Gustav Johannessen, Mona Hegstad, Kristin Nizet, Victor Askarian, Fatemeh |
author_sort | Kumaraswamy, Monika |
collection | PubMed |
description | Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures. |
format | Online Article Text |
id | pubmed-8539228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85392282021-10-24 Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus Kumaraswamy, Monika Wiull, Kamilla Joshi, Bishnu Sakoulas, George Kousha, Armin Vaaje-Kolstad, Gustav Johannessen, Mona Hegstad, Kristin Nizet, Victor Askarian, Fatemeh Microorganisms Article Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures. MDPI 2021-09-29 /pmc/articles/PMC8539228/ /pubmed/34683376 http://dx.doi.org/10.3390/microorganisms9102055 Text en © 2021 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 Kumaraswamy, Monika Wiull, Kamilla Joshi, Bishnu Sakoulas, George Kousha, Armin Vaaje-Kolstad, Gustav Johannessen, Mona Hegstad, Kristin Nizet, Victor Askarian, Fatemeh Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title | Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title_full | Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title_fullStr | Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title_full_unstemmed | Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title_short | Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus |
title_sort | bacterial membrane-derived vesicles attenuate vancomycin activity against methicillin-resistant staphylococcus aureus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539228/ https://www.ncbi.nlm.nih.gov/pubmed/34683376 http://dx.doi.org/10.3390/microorganisms9102055 |
work_keys_str_mv | AT kumaraswamymonika bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT wiullkamilla bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT joshibishnu bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT sakoulasgeorge bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT koushaarmin bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT vaajekolstadgustav bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT johannessenmona bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT hegstadkristin bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT nizetvictor bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus AT askarianfatemeh bacterialmembranederivedvesiclesattenuatevancomycinactivityagainstmethicillinresistantstaphylococcusaureus |