Open Access Research

The multidrug-resistant PMEN1 pneumococcus is a paradigm for genetic success

Kelly L Wyres1, Lotte M Lambertsen2, Nicholas J Croucher3, Lesley McGee4, Anne von Gottberg5, Josefina Liñares6, Michael R Jacobs7, Karl G Kristinsson8, Bernard W Beall4, Keith P Klugman9, Julian Parkhill3, Regine Hakenbeck10, Stephen D Bentley3 and Angela B Brueggemann1*

Author affiliations

1 Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK

2 Department of Microbiology Surveillance and Research, Statens Serum Institut, 5 Artillerivej, DK 2300 Copenhagen S, Denmark

3 Pathogen Genomics Team, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

4 Streptococcus Laboratory, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, Georgia, 30333, USA

5 Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Sandringham, Johannesburg 2131, South Africa

6 Department of Microbiology, Bellvitge Hospital-CIBERes-IDIBELL-UB, Feixa Llarga s/n, 08907 Barcelona, Spain

7 Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA

8 Clinical Microbiology Department, Landspitali University Hospital and University of Iceland, 101 Reykjavik, Iceland

9 Hubert Department of Global Health Epidemiology, Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA 30322, USA

10 Department of Microbiology, University Kaiserslautern, Paul-Ehrlich-Straße, 67663 Kaiserslautern, Germany

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Citation and License

Genome Biology 2012, 13:R103  doi:10.1186/gb-2012-13-11-r103

Published: 16 November 2012

Abstract

Background

Streptococcus pneumoniae, also called the pneumococcus, is a major bacterial pathogen. Since its introduction in the 1940s, penicillin has been the primary treatment for pneumococcal diseases. Penicillin resistance rapidly increased among pneumococci over the past 30 years, and one particular multidrug-resistant clone, PMEN1, became highly prevalent globally. We studied a collection of 426 pneumococci isolated between 1937 and 2007 to better understand the evolution of penicillin resistance within this species.

Results

We discovered that one of the earliest known penicillin-nonsusceptible pneumococci, recovered in 1967 from Australia, was the likely ancestor of PMEN1, since approximately 95% of coding sequences identified within its genome were highly similar to those of PMEN1. The regions of the PMEN1 genome that differed from the ancestor contained genes associated with antibiotic resistance, transmission and virulence. We also revealed that PMEN1 was uniquely promiscuous with its DNA, donating penicillin-resistance genes and sometimes many other genes associated with antibiotic resistance, virulence and cell adherence to many genotypically diverse pneumococci. In particular, we describe two strains in which up to 10% of the PMEN1 genome was acquired in multiple fragments, some as long as 32 kb, distributed around the recipient genomes. This type of directional genetic promiscuity from a single clone to numerous unrelated clones has, to our knowledge, never before been described.

Conclusions

These findings suggest that PMEN1 is a paradigm of genetic success both through its epidemiology and promiscuity. These findings also challenge the existing views about horizontal gene transfer among pneumococci.