A surprise finisher in the genome stakes last month was the Lancet publication of the complete sequence of two Staphylococcus aureus strains by Kuroda and colleagues from Japan's Juntendo University 1xWhole genome sequencing of meticillin-resistance Staphylococcus aureus. Kuroda, M. et al. Lancet. 2001; 357: 1225–1240Abstract | Full Text | Full Text PDF | PubMed | Scopus (1217)See all References. The paper gives a comprehensive description of the genome sequences of a recent Japanese-derived methicillin-resistant S. aureus (MRSA; N315; 2.8 Mb) and a closely related vancomycin-resistant MRSA strain (Mu50; 2.9 Mb), and the comparison between them. Genome sequencing projects are generally trailed well in advance of completion, and are usually accompanied by early data release, so the appearance of an almost entirely unexpected complete genome (or even two!) is quite unusual. Highlights of the paper include the description of three new classes of pathogenicity islands: a toxic-shock-syndrome toxin island family, exotoxin islands and endotoxin islands, and several candidates for new virulence factors. The authors ascribe the virulence of these two strains to the lateral acquisition of genes from many other different species and the extreme diversity of superantigens. They correlate these findings with the ability of S. aureus to adapt to environmental pressures such as antibiotics and the human immune system.The analysis includes a comparison with the most similar bacterial genome described to date, Bacillus subtilis (4.2 Mb): up to 52% of the predicted proteins are similar in both, although most of these are involved in essential functions. Obviously S. aureus lacks the sporulation and rod-shape morphogenesis genes present in B. subtilis, and copes with only two sigma factors, sigA and sigB, in contrast to B. subtilis, which uses 20 or more. It is interesting to note that among the bacterial species whose genomes have been completely sequenced, the third most closely related to S. aureus is the non-pathogenic bacterium Lactococcus lactis.Other S. aureus genome projects in progress include that of COL, an early MRSA strain, at TIGR (http://www.tigr.org); 8325, the commonly used laboratory strain at the University of Oklahoma (http://www.genome.ou.edu/staph.html) and two recently isolated MRSA and methicillin-sensitive S. aureus (MSSA) strains at The Sanger Centre (http://www.sanger.ac.uk/Projects/S_aureus). The spread of different times of isolation and resistance carriage by these six strains should allow a great deal of information on the evolution of this important organism to be gleaned from the comparisons between them.Keeping with the Gram-positive theme, Ferretti and colleagues at Oklahoma 2xComplete genome sequence of an M1 strain of Streptococcus pyogenes. Ferretti, J.J. et al. Proc. Natl. Acad. Sci. U. S. A. 2001; 9: 4658–4663Crossref | Scopus (687)See all References, and Bolotin and colleagues at Genoscope 3xThe complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lactis IL1403. Bolotin, A. et al. Genome Res. 2001; 11: 731–753Crossref | PubMed | Scopus (769)See all References have recently reported the complete genome sequences of two important Gram-positive lactic acid bacteria: the strictly human pathogen Streptococcus pyogenes (1.8 Mb), a group A streptococci (GAS), and its non-pathogenic close relative Lactococcus lactis ssp. lactis (LAB; 2.4 Mb), respectively. GAS is the causative agent of a wide range of diseases (more than any other pathogen), including scarlet fever, impetigo and necrotizing fasciitis, whereas LAB is a harmless microorganism used for milk fermentation and cheese production. LAB has been successfully used as a model system for the study of the physiology and genetics of all lactic-acid bacteria and will now be an invaluable resource for comparing its gene inventory with its other, more pathogenic relatives; in effect acting as a negative control for the genomic study of pathogenicity. Like GAS, LAB lacks a complete tricarboxylic acid cycle, consistent with the notion that these bacteria are exclusively fermentative. Surprisingly, however, the genome sequence of LAB has revealed the presence of several genes required for aerobic respiration, information that could be used to optimize the industrial applications of this bacterium.Although natural competence had not been demonstrated for either LAB or GAS, multiple genes showing high similarity to competence-associated genes from other Gram-positive and Gram-negative bacteria have been identified in both genetic backgrounds, and there is some evidence for the transfer of DNA between lactococci. It is estimated that bacteriophage and transposon genes account for ∼10% of their total genomes, suggesting that this is also a significant source of laterally acquired DNA; indeed, three of the four identified prophage in S. pyogenes were shown to be carrying genes encoding virulence-associated proteins, each sitting neatly in a low-G+C region at the end of the phage. Interestingly, although 40 putative virulence-associated genes were identified in GAS, none of these genes cluster within pathogenicity islands, unlike in many other pathogens such as MRSA. As with MRSA, and indeed most other important bacterial pathogens, comparative sequencing of other S. pyogenes strains is already under way (http://www.sanger.ac.uk/Projects/S_pyogenes).