Genome sequencing unveils a novel sea enterotoxin-carrying PVL phage in Staphylococcus aureus ST772 from India

PLoS One. 2013;8(3):e60013. doi: 10.1371/journal.pone.0060013. Epub 2013 Mar 27.

Abstract

Staphylococcus aureus is a major human pathogen, first recognized as a leading cause of hospital-acquired infections. Community-associated S. aureus (CA-SA) pose a greater threat due to increase in severity of infection and disease among children and healthy adults. CA-SA strains in India are genetically diverse, among which is the sequence type (ST) 772, which has now spread to Australia, Europe and Japan. Towards understanding the genetic characteristics of ST772, we obtained draft genome sequences of five relevant clinical isolates and studied the properties of their PVL-carrying prophages, whose presence is a defining hallmark of CA-SA. We show that this is a novel prophage, which carries the structural genes of the hlb-carrying prophage and includes the sea enterotoxin. This architecture probably emerged early within the ST772 lineage, at least in India. The sea gene, unique to ST772 PVL, despite having promoter sequence characteristics typical of low expression, appears to be highly expressed during early phase of growth in laboratory conditions. We speculate that this might be a consequence of its novel sequence context. The crippled nature of the hlb-converting prophage in ST772 suggests that widespread mobility of the sea enterotoxin might be a selective force behind its 'transfer' to the PVL prophage. Wild type ST772 strains induced strong proliferative responses as well as high cytotoxic activity against neutrophils, likely mediated by superantigen SEA and the PVL toxin respectively. Both proliferation and cytotoxicity were markedly reduced in a cured ST772 strain indicating the impact of the phage on virulence. The presence of SEA alongside the genes for the immune system-modulating PVL toxin may contribute to the success and virulence of ST772.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Base Sequence
  • Enterotoxins / genetics
  • Enterotoxins / metabolism*
  • Exotoxins / genetics
  • Exotoxins / metabolism*
  • Genome, Bacterial / genetics*
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Humans
  • India
  • Leukocidins / genetics
  • Leukocidins / metabolism*
  • Molecular Sequence Data
  • Prophages / metabolism*
  • Prophages / ultrastructure
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA*
  • Sphingomyelin Phosphodiesterase / genetics
  • Sphingomyelin Phosphodiesterase / metabolism
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / ultrastructure
  • Staphylococcus aureus / virology*

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Exotoxins
  • Hemolysin Proteins
  • Leukocidins
  • Panton-Valentine leukocidin
  • RNA, Messenger
  • enterotoxin A, Staphylococcal
  • Sphingomyelin Phosphodiesterase
  • hlb protein, Staphylococcus aureus

Grant support

SP is a junior research fellow under BT/IN/New Indigo/16/GA/2010. SK is supported by fellowship [09/860(0122)/2011-EMR-I] from the Council for Scientific & Industrial Research (CSIR), India. ASNS is funded by the NCBS core budget and the Ramanujan Fellowship (SR/S2/RJN-49/2010) from the Department of Science and Technology, Government of India. GA is funded by Department of Biotechnology (BT/IN/New Indigo/16/GA/2010) and Swedish International Development Agency funding to ANT and GA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.