Signatures of cytoplasmic proteins in the exoproteome distinguish community- and hospital-associated methicillin-resistant Staphylococcus aureus USA300 lineages

Research output: Contribution to journalJournal articlepeer-review

  • Solomon A. Mekonnen
  • Laura M. Palma Medina
  • Corinna Glasner
  • Eleni Tsompanidou
  • Anne de Jong
  • Stefano Grasso
  • Marc Schaffer
  • Ulrike Mäder
  • Anders R. Larsen
  • Heidi Gumpert
  • Westh, Henrik T.
  • Uwe Völker
  • Andreas Otto
  • Dörte Becher
  • Jan Maarten van Dijl

Methicillin-resistant Staphylococcus aureus (MRSA) is the common name for a heterogeneous group of highly drug-resistant staphylococci. Two major MRSA classes are distinguished based on epidemiology, namely community-associated (CA) and hospital-associated (HA) MRSA. Notably, the distinction of CA- and HA-MRSA based on molecular traits remains difficult due to the high genomic plasticity of S. aureus. Here we sought to pinpoint global distinguishing features of CA- and HA-MRSA through a comparative genome and proteome analysis of the notorious MRSA lineage USA300. We show for the first time that CA- and HA-MRSA isolates can be distinguished by 2 distinct extracellular protein abundance clusters that are predictive not only for epidemiologic behavior, but also for their growth and survival within epithelial cells. This ‘exoproteome profiling’ also groups more distantly related HA-MRSA isolates into the HA exoproteome cluster. Comparative genome analysis suggests that these distinctive features of CA- and HA-MRSA isolates relate predominantly to the accessory genome. Intriguingly, the identified exoproteome clusters differ in the relative abundance of typical cytoplasmic proteins, suggesting that signatures of cytoplasmic proteins in the exoproteome represent a new distinguishing feature of CA- and HA-MRSA. Our comparative genome and proteome analysis focuses attention on potentially distinctive roles of ‘liberated’ cytoplasmic proteins in the epidemiology and intracellular survival of CA- and HA-MRSA isolates. Such extracellular cytoplasmic proteins were recently invoked in staphylococcal virulence, but their implication in the epidemiology of MRSA is unprecedented.

Original languageEnglish
Issue number6
Pages (from-to)891-907
Number of pages17
Publication statusPublished - 2017

    Research areas

  • community, epithelial cells, exoproteome, hospital, moonlighting, MRSA, protein secretion, Staphylococcus, USA300, virulence factor

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