Sun, 27 Jul 2008 06:11:05 BST CiteULike: Xavier's Bruce http://www.citeulike.org/user/Xavier/author/Bruce CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/Xavier/article/2485534 <i>PLoS ONE, Vol. 2, No. 9. (2007)</i><br /><br />Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I - A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between "WY96" and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis. Complete Genomic Characterization of a Pathogenic A.II Strain of Francisella tularensis Subspecies tularensis. SM Beckstrom-Sternberg RK Auerbach S Godbole JV Pearson JS Beckstrom-Sternberg Z Deng C Munk K Kubota Y Zhou D Bruce J Noronha RH Scheuermann A Wang X Wei J Wang J Hao DM Wagner TS Brettin N Brown P Gilna PS Keim doi:10.1371/journal.pone.0000947 PLoS ONE, Vol. 2, No. 9. (2007) 2008-03-07T16:29:56-00:00 2007 PLoS ONE 1932-6203 2 9 frank http://www.citeulike.org/user/Xavier/article/1430602 <i>Proc Natl Acad Sci U S A, Vol. 104, No. 22. (29 May 2007), pp. 9451-9456.</i><br /><br />The spread of multidrug-resistant Staphylococcus aureus (MRSA) strains in the clinical environment has begun to pose serious limits to treatment options. Yet virtually nothing is known about how resistance traits are acquired in vivo. Here, we apply the power of whole-genome sequencing to identify steps in the evolution of multidrug resistance in isogenic S. aureus isolates recovered periodically from the bloodstream of a patient undergoing chemotherapy with vancomycin and other antibiotics. After extensive therapy, the bacterium developed resistance, and treatment failed. Sequencing the first vancomycin susceptible isolate and the last vancomycin nonsusceptible isolate identified genome wide only 35 point mutations in 31 loci. These mutations appeared in a sequential order in isolates that were recovered at intermittent times during chemotherapy in parallel with increasing levels of resistance. The vancomycin nonsusceptible isolates also showed a 100-fold decrease in susceptibility to daptomycin, although this antibiotic was not used in the therapy. One of the mutated loci associated with decreasing vancomycin susceptibility (the vraR operon) was found to also carry mutations in six additional vancomycin nonsusceptible S. aureus isolates belonging to different genetic backgrounds and recovered from different geographic sites. As costs drop, whole-genome sequencing will become a useful tool in elucidating complex pathways of in vivo evolution in bacterial pathogens. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. MM Mwangi SW Wu Y Zhou K Sieradzki H de Lencastre P Richardson D Bruce E Rubin E Myers ED Siggia A Tomasz doi:10.1073/pnas.0609839104 Proc Natl Acad Sci U S A, Vol. 104, No. 22. (29 May 2007), pp. 9451-9456. 2007-07-03T11:46:27-00:00 2007 Proc Natl Acad Sci U S A 0027-8424 104 22 9451 9456 staph