Sequential #evolution of #virulence and #resistance during clonal spread of community-acquired #MRSA (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Sequential evolution of virulence and resistance during clonal spread of community-acquired methicillin-resistant Staphylococcus aureus

Richard Copin, William E. Sause, Yi Fulmer, Divya Balasubramanian, Sophie Dyzenhaus, Jamil M. Ahmed, Krishan Kumar, John Lees, Anna Stachel, Jason C. Fisher, Karl Drlica, Michael Phillips, Jeffrey N. Weiser, Paul J. Planet, Anne-Catrin Uhlemann, Deena R. Altman, Robert Sebra, Harm van Bakel, Jennifer Lighter, Victor J. Torres, and Bo Shopsin

PNAS published ahead of print January 11, 2019 / DOI:

Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved December 6, 2018 (received for review August 17, 2018)



Epidemics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are of growing medical concern. To understand the emergence of virulence and antimicrobial resistance, both of which promote CA-MRSA spread, we examined an on-going disease cluster within an enclosed community by analyzing the genome sequences of CA-MRSA clones characterized by high prevalence and a profound persistence. Metabolic adaptation and a phage primed the clone for success, and then a fully optimized variant was created by selection of plasmid-mediated biocide resistance. The data provide mechanistic insight and indicate that high-risk populations are incubators for evolution of consequential phenotypes. Immediate interruption of this evolutionary pattern is essential for forestalling dissemination of resistance from high-risk communities to hospitals and the general population.



The past two decades have witnessed an alarming expansion of staphylococcal disease caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The factors underlying the epidemic expansion of CA-MRSA lineages such as USA300, the predominant CA-MRSA clone in the United States, are largely unknown. Previously described virulence and antimicrobial resistance genes that promote the dissemination of CA-MRSA are carried by mobile genetic elements, including phages and plasmids. Here, we used high-resolution genomics and experimental infections to characterize the evolution of a USA300 variant plaguing a patient population at increased risk of infection to understand the mechanisms underlying the emergence of genetic elements that facilitate clonal spread of the pathogen. Genetic analyses provided conclusive evidence that fitness (manifest as emergence of a dominant clone) changed coincidently with the stepwise emergence of (i) a unique prophage and mutation of the regulator of the pyrimidine nucleotide biosynthetic operon that promoted abscess formation and colonization, respectively, thereby priming the clone for success; and (ii) a unique plasmid that conferred resistance to two topical microbiocides, mupirocin and chlorhexidine, frequently used for decolonization and infection prevention. The resistance plasmid evolved through successive incorporation of DNA elements from non-S. aureus spp. into an indigenous cryptic plasmid, suggesting a mechanism for interspecies genetic exchange that promotes antimicrobial resistance. Collectively, the data suggest that clonal spread in a vulnerable population resulted from extensive clinical intervention and intense selection pressure toward a pathogen lifestyle that involved the evolution of consequential mutations and mobile genetic elements.

MRSA – evolution – antimicrobial resistance – virulence



1 R.C. and W.E.S. contributed equally to this work.

2 To whom correspondence may be addressed. Email:,, or

Author contributions: R.C., W.E.S., J. Lighter, V.J.T., and B.S. designed research; R.C., W.E.S., Y.F., D.B., S.D., J.M.A., K.K., A.S., J.C.F., M.P., and D.R.A. performed research; R.C., J. Lees, P.J.P., A.-C.U., R.S., and H.v.B. contributed new reagents/analytic tools; R.C., W.E.S., D.B., and S.D. analyzed data; and R.C., W.E.S., K.D., J.N.W., V.J.T., and B.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: All genomic data reported in this paper have been deposited in the National Center for Biotechnology Information BioProject database (accession no. PRJNA497094).

This article contains supporting information online at

Published under the PNAS license.

Keywords: Antibiotics; Drugs Resistance; Mupirocin; Chlorhexidine; MRSA; CA-MRSA; Staphylococcus aureus.


Published by

Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum ( in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.