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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.00082

Local diversification of methicillin-resistant Staphylococcus aureus ST239 in South America after its rapid worldwide dissemination

  • 1Laboratório de Biologia Molecular de Bactérias, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro,, Brazil
  • 2Laboratório Nacional de Computação Científica (LNCC), Brazil
  • 3Department of Pediatrics, Division of Pediatric Infectious Diseases, Children’s Hospital of Philadelphia & University of Pennsylvania, United States
  • 4Universidade Federal do Rio de Janeiro, Brazil
  • 5Sackler Institute for Comparative Genomics, American Museum of Natural History, United States
  • 6Department of Epidemiology and Biostatistics, School of Public Health, SUNY Downstate Medical Center, United States

The global spread of specific clones of methicillin-resistant S. aureus (MRSA) has become a major public health problem, and understanding the dynamics of geographical spread requires worldwide surveillance. Over the past 20 years, the ST239 lineage of MRSA has been recognized as an emerging clone across the globe, with detailed studies focusing on isolates from Europe and Asia. Less is known about this lineage in South America, and, particularly, Brazil where it was the predominant lineage of MRSA in the early 1990’s to 2000’s. To gain a better understanding about the introduction and spread of ST239 MRSA in Brazil we undertook a comparative phylogenomic analysis of ST239 genomes, adding 7 completed, closed Brazilian genomes. Brazilian ST239 isolates grouped in a subtree with those from South American and Western European countries, designated the South American clade. After an initial worldwide radiation in the 1960 to 1970’s, we estimate that ST239 began to spread in South America and Brazil in approximately 1988. This clone demonstrates specific genomic changes that are suggestive of local divergence and adaptational change including agrC variants, and a distinct pattern of virulence-associated genes (the presence of the chp and the absence of sea and sasX). A survey of a geographically and chronologically diverse set of 100 Brazilian ST239 isolates identified this virulence genotype as the predominant pattern in Brazil, and uncovered an unexpectedly high prevalence of agr-dysfunction (30%). ST239 isolates from Brazil also appear to have undergone transposon (IS256) insertions in or near global regulatory genes (agr and mgr) that likely led to rapid reprogramming of bacterial traits. In general, the overall pattern observed in phylogenomic analyses of ST239 is of a rapid initial global radiation,with subsequent local spread and adaptation in multiple different geographic locations. Most ST239 isolates harbor the ardA gene, which we show here to have in vivo anti-restriction activity. We hypothesize that this gene may have improved the ability of this lineage to acquire multiple resistance genes and distinct virulence-associated genes in each local context. The allopatric divergence pattern of ST239 also may suggest strong selective pressures for specific traits in different geographical locations.

Keywords: phylogenetic analysis, whole genome sequencing, South - America, MRSA, Brazil

Received: 18 Aug 2018; Accepted: 16 Jan 2019.

Edited by:

Steven Tong, Peter Doherty Institute for Infection and Immunity, Australia

Reviewed by:

Santiago Castillo Ramírez, National Autonomous University of Mexico, Mexico
Sarah L. Baines, The University of Melbourne, Australia
Sebastiaan Van Hal, Royal Prince Alfred Hospital, Australia
Davida Smyth, The New School, United States  

Copyright: © 2019 Botelho, Oliveira Cerqueira e Costa, Moustafa, Beltrame, Ferreira, Côrtes, Souza, Nascimento, Bandeira, Barros Lima, Souza, Almeida, Vasconcelos, Narechania, Ryan, O'Brien, Kolokotronis, Planet, NICOLÁS and Figueiredo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Paul J. Planet, Department of Pediatrics, Division of Pediatric Infectious Diseases, Children’s Hospital of Philadelphia & University of Pennsylvania, Philadelphia, United States, planetp@email.chop.edu
Dr. MARISA F. NICOLÁS, Laboratório Nacional de Computação Científica (LNCC), Petrópolis, Rio de Janeiro, Brazil, marisa@lncc.br
Prof. Agnes M. Figueiredo, Laboratório de Biologia Molecular de Bactérias, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro,, Rio de Janeiro, Brazil, agnes@micro.ufrj.br