Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-ResistantStaphylococcus aureusInfections

Autor: Joshua N. Adkins, Suzanna Gore, Justine K. Rudkin, Tim Downing, Simone Coughlan, Eoghan O'Neill, Guoqing Xia, Aras Kadioglu, James P. O'Gara, Elaine M. Waters, Nikki S. Black, Geremy Clair
Rok vydání: 2016
Předmět:
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine
medicine.drug_class
Cost effectiveness
vancomycin
030106 microbiology
Antibiotics
Virulence
panton-valentine leukocidin
Microbial Sensitivity Tests
medicine.disease_cause
Microbiology
Sepsis
Mice
03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
antibiotic
Pneumonia
Staphylococcal
Animals
Humans
Immunology and Allergy
Medicine
bacteremia
genes
Pathogen
attenuation
Oxacillin
combination
therapy
business.industry
Quorum Sensing
Gene Expression Regulation
Bacterial
Staphylococcal Infections
biochemical phenomena
metabolism
and nutrition
medicine.disease
Methicillin-resistant Staphylococcus aureus
Anti-Bacterial Agents
Disease Models
Animal
030104 developmental biology
Infectious Diseases
Staphylococcus aureus
mrsa
Methicillin Resistance
beta-lactam
business
Zdroj: Waters, E M, Rudkin, J K, Coughlan, S, Clair, G C, Adkins, J N, Gore, S, Xia, G, Black, N S, Downing, T, O'Neill, E, Kadioglu, A & O'Gara, J P 2017, ' Redeploying β-lactam antibiotics as a novel antivirulence strategy for the treatment of methicillin-resistant Staphylococcus aureus infections ', Journal of INfectious Diseases, vol. 215, no. 1, pp. 80-87 . https://doi.org/10.1093/infdis/jiw461
ISSN: 1537-6613
0022-1899
Popis: Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobialresistance crisis. We report a new approach to the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infectionsby demonstrating that oxacillin can be used to significantly attenuate the virulence of MRSA despite the pathogen being resistantto this drug. Using mechanistic in vitro assays and in vivo models of invasive pneumonia and sepsis, we show that oxacillin treated MRSAstrains are significantly attenuated in virulence. This effect is based primarily on the oxacillin-dependent repressionof the accessory gene regulator quorum-sensing system and altered cell wall architecture, which in turn lead to increased susceptibilityto host killing of MRSA. Our data indicate that β-lactam antibiotics should be included in the treatment regimen as anadjunct antivirulence therapy for patients with MRSA infections. This would represent an important change to current clinicalpractice for treatment of MRSA infection, with the potential to significantly improve patient outcomes in a safe, cost-effectivemanner.Keywords. MRSA; antibiotic; beta-lactam; virulence; attenuation.
Databáze: OpenAIRE
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