Whole genome sequencing of meticillin-resistant Staphylococcus aureus.

By M. Kuroda, T. Ohta, I. Uchiyama, T. Baba, H. Yuzawa, I. Kobayashi, L. Cui, A. Oguchi, Ken-ichi Aoki, Y. Nagai and 27 more. The Lancet, 2001

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BACKGROUND Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism. METHODS Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction. FINDINGS The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors. INTERPRETATION The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.

Subfields: Infectious Diseases, Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/17541644f9332e88224dc9300cb207db565ebaab

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Citations in the corpus

Increasing biological complexity is positively correlated with the relative genome-wide expansion of non-protein-coding DNA sequences (2003, neutral): “157 2708 5076187 [101] Bacillus anthracis 0.159 5842 5370060 [103] Bacillus cereus 0.16 5366 546909 [104] Buchnera aphidicola (Bp) 0.164 553 618000 [105] Staphylococcus aureus N315 0.165 2595 2813641 [106] Staphylococcus aureus Mu50 0.169 2687 2878084 [106] Clostridium perfringens 0.169 2660 3031430”
Pathogenicity Islands in Bacterial Pathogenesis (2004, background): “coli O157:H7 strains by two groups in the United States and Japan, and the genomes were published in 2001 (200, 271).”
Staphylococcus and biofilms (2002, background): “The recently sequenced genomes of S. aureus N315 and Mu50 contain, in addition to prophages and various transposons, 10 copies of IS1181 and two of IS431, distributed over the genome (Kuroda et al., 2001).”
The Genera Staphylococcus and Macrococcus (2006, methodology): “…Both annotated S. aureus N315 and Mu50 genomes contain a so-called “staphylococcal cassette chromosome mec” (SCCmec) which encodes resistance to β-lactams, bleomycin, macrolide-lincosamide streptogramin B, aminoglycosides (tobramycin and amikacin), and spectinomycin (Kuroda et al., 2001).”
Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology (2018, background): “SCCmec type II was first described in 1999 in the characteristic MRSA strain N315 and is found predominantly in HA-MRSA strains.”