Wed, 20 Aug 2008 22:04:27 BST CiteULike: Xavier's Aoki http://www.citeulike.org/user/Xavier/author/Aoki CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/Xavier/article/2465197 <i>Lancet, Vol. 359, No. 9320. (25 May 2002), pp. 1819-1827.</i><br /><br />BACKGROUND: A new type of meticillin-resistant Staphylococcus aureus (MRSA), designated community-acquired MRSA, is becoming increasingly noticeable in the community, some strains of which cause fatal infections in otherwise healthy individuals. By contrast with hospital-acquired MRSA, community-acquired MRSA is more susceptible to non b-lactam antibiotics. We investigated the high virulence potential of certain strains of this bacterium. METHODS: We ascertained the whole genome sequence of MW2, a strain of community-acquired MRSA, by shotgun cloning and sequencing. MW2 caused fatal septicaemia and septic arthritis in a 16-month-old girl in North Dakota, USA, in 1998. The genome of this strain was compared with those of hospital-acquired MRSA strains, including N315 and Mu50. FINDINGS: Meticillin resistance gene (mecA) in MW2 was carried by a novel allelic form (type IVa) of staphylococcal cassette chromosome mec (SCCmec), by contrast with type II in N315 and Mu50. Type IVa SCCmec did not carry any of the multiple antibiotic resistance genes reported in type II SCCmec. By contrast, 19 additional virulence genes were recorded in the MW2 genome. All but two of these virulence genes were noted in four of the seven genomic islands of MW2. INTERPRETATION: MW2 carried a range of virulence and resistance genes that was distinct from those displayed on the chromosomes of extant S aureus strains. Most genes were carried by specific allelic forms of genomic islands in the MW2 chromosome. The combination of allelic forms of genomic islands is the genetic basis that determines the pathogenicity of medically important phenotypes of S aureus, including those of community-acquired MRSA strains. Genome and virulence determinants of high virulence community-acquired MRSA. T Baba F Takeuchi M Kuroda H Yuzawa K Aoki A Oguchi Y Nagai N Iwama K Asano T Naimi H Kuroda L Cui K Yamamoto K Hiramatsu Lancet, Vol. 359, No. 9320. (25 May 2002), pp. 1819-1827. 2008-03-04T15:55:21-00:00 2002 Lancet 0140-6736 359 9320 1819 1827 staph http://www.citeulike.org/user/Xavier/article/2465196 <i>Lancet, Vol. 357, No. 9264. (21 April 2001), pp. 1225-1240.</i><br /><br />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. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. M Kuroda T Ohta I Uchiyama T Baba H Yuzawa I Kobayashi L Cui A Oguchi K Aoki Y Nagai J Lian T Ito M Kanamori H Matsumaru A Maruyama H Murakami A Hosoyama Y Mizutani-Ui NK Takahashi T Sawano R Inoue C Kaito K Sekimizu H Hirakawa S Kuhara S Goto J Yabuzaki M Kanehisa A Yamashita K Oshima K Furuya C Yoshino T Shiba M Hattori N Ogasawara H Hayashi K Hiramatsu Lancet, Vol. 357, No. 9264. (21 April 2001), pp. 1225-1240. 2008-03-04T15:55:14-00:00 2001 Lancet 0140-6736 357 9264 1225 1240 staph