(精选)bacteria subsisting on antibiotics教学课件.pptVIP

Bacteria Subsisting on Antibiotics Gautam Dantas Church Lab CEGS Annual Grantee Meeting - 2008 Agency for healthcare research and quality, 2006 US reported MRSA infections [1000’s] in US: MRSA kills more people than AIDS 2006: 18,964 2006: 14,627 Mechanisms of antibiotic resistance antibiotic modification efflux target modification resistance gene origin hypothesis: antibiotic resistance genes originated as producer self immunity and was transferred to human pathogens Proc. Nat. Acad. Sci. 70:2276 (1973) Science 312:374 (2006) many antibiotics are produced in the environment, but it is likely that they undergo further biological transformations  G. Dantas., M. Sommer et al. Science 320:100 (2008) GROWTH NO GROWTH Bacteria subsisting on antibiotics are widely distributed in the environment Antibiotic eaters are phylogenetically diverse G. Dantas., M. Sommer et al. Science 320:100 (2008) using functional genomic selections we have identified more than 150 unique antibiotic resistance genes from antibiotic eaters Gentamicin resistance from eater vs. Salmonella enterica subsp. enterica serovar Typhimurium genomic island I Experiments by: G. Dantas, M. Sommer. Unpublished data resistance genes from some antibiotic catabolizers are identical to resistance genes of pathogens at the nucleotide level best genetic support for producer hypothesis: gigb|AY082011.1| Enterococcus faecium strain 10/96A vanD gene cluster, complete sequence; and ISEfa4 insertion sequence elementgi|4104707:67-693 Streptomyces toyocaensis D-ala-D-ala dipeptidase (vanXst) gene, complete cds; and unknown gene ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 42: 2215 (1998), Science 312:374 (2006), Nature Reviews Microbiology 5:175 (2007) Producer vs. Pathogen best homology between resistance gene from producer and pathogen: 66% identity @ nucleotide level homology between resistance gene from eater and pathogen: 98.5%, 99.9%, 99.9%, 100% identity @ nucleotide level some antibiotic r