Taj Azarian1, Robert S Daum2, Lindsay A Petty3, Jenny L Steinbeck3, Zachary Yin2, David Nolan4, Susan Boyle-Vavra2, W P Hanage1, Marco Salemi4, Michael Z David5. 1. Center for Communicable Disease Dynamics, Department of Epidemiology, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts. 2. Department of Pediatrics. 3. Department of Medicine, University of Chicago, Illinois. 4. Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine Emerging Pathogens Institute, University of Florida, Gainesville. 5. Department of Pediatrics Department of Medicine, University of Chicago, Illinois.
Abstract
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks. METHODS: To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3-6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29). RESULTS: Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population. DISCUSSIONS: During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling.
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks. METHODS: To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3-6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29). RESULTS: Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population. DISCUSSIONS: During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling.
Authors: Kelsi L Anderson; Corbette Roberts; Terrence Disz; Veronika Vonstein; Kaitlyn Hwang; Ross Overbeek; Patrick D Olson; Steven J Projan; Paul M Dunman Journal: J Bacteriol Date: 2006-10 Impact factor: 3.490
Authors: Md Tauqeer Alam; Timothy D Read; Robert A Petit; Susan Boyle-Vavra; Loren G Miller; Samantha J Eells; Robert S Daum; Michael Z David Journal: mBio Date: 2015-03-10 Impact factor: 7.867
Authors: James R Price; Tanya Golubchik; Kevin Cole; Daniel J Wilson; Derrick W Crook; Guy E Thwaites; Rory Bowden; A Sarah Walker; Timothy E A Peto; John Paul; Martin J Llewelyn Journal: Clin Infect Dis Date: 2013-12-12 Impact factor: 9.079
Authors: Ross Overbeek; Robert Olson; Gordon D Pusch; Gary J Olsen; James J Davis; Terry Disz; Robert A Edwards; Svetlana Gerdes; Bruce Parrello; Maulik Shukla; Veronika Vonstein; Alice R Wattam; Fangfang Xia; Rick Stevens Journal: Nucleic Acids Res Date: 2013-11-29 Impact factor: 16.971
Authors: Inês R Grilo; Ana Madalena Ludovice; Alexander Tomasz; Hermínia de Lencastre; Rita G Sobral Journal: Microbiologyopen Date: 2014-03-03 Impact factor: 3.139
Authors: Nicholas A Turner; Batu K Sharma-Kuinkel; Stacey A Maskarinec; Emily M Eichenberger; Pratik P Shah; Manuela Carugati; Thomas L Holland; Vance G Fowler Journal: Nat Rev Microbiol Date: 2019-04 Impact factor: 60.633
Authors: Amaya Campillay Lagos; Martin Sundqvist; Fredrik Dyrkell; Marc Stegger; Bo Söderquist; Paula Mölling Journal: Sci Rep Date: 2022-06-22 Impact factor: 4.996
Authors: Eugene V Millar; Gregory K Rice; Emad M Elassal; Carey D Schlett; Jason W Bennett; Cassie L Redden; Deepika Mor; Natasha N Law; David R Tribble; Theron Hamilton; Michael W Ellis; Kimberly A Bishop-Lilly Journal: Clin Infect Dis Date: 2017-08-01 Impact factor: 9.079
Authors: Catriona P Harkins; Kerry A Pettigrew; Katarina Oravcová; June Gardner; R M Ross Hearn; Debbie Rice; Alison E Mather; Julian Parkhill; Sara J Brown; Charlotte M Proby; Matthew T G Holden Journal: J Invest Dermatol Date: 2017-09-23 Impact factor: 8.551
Authors: Sion C Bayliss; David W Verner-Jeffreys; Kerry L Bartie; David M Aanensen; Samuel K Sheppard; Alexandra Adams; Edward J Feil Journal: Front Microbiol Date: 2017-02-03 Impact factor: 5.640