Comparative Genome Analysis of the Daptomycin-Resistant Streptococcus anginosus Strain J4206 Associated with Breakthrough Bacteremia.
Streptococcus anginosus is a member of the normal oral flora that can become a pathogen causing pyogenic infections in humans. The genome of daptomycin-resistant strain J4206, originally isolated from a patient suffering from breakthrough bacteremia and septic shock at the University of Texas Health Science Center at San Antonio, was determined. The circular genome is 2,001,352 bp long with a GC content of 38.62% and contains multiple mobile genetic elements, including the phage-like chromosomal island SanCI that mediates a mutator phenotype, transposons, and integrative conjugative elements. Daptomycin resistance involves multiple alterations in the cell membrane and cell wall, and unique features were identified in J4206 that may contribute to resistance. A cluster of capsular polysaccharide (CPS) genes for choline metabolism and transport are present that may help neutralize cell surface charges, destabilizing daptomycin binding. Further, unique J4206 genes encoding sortases and LPXTG-target proteins that are involved in cell wall modification were present. The J4206 genome is phylogenetically closely related to the recently reported vancomycin-resistant SA1 strain; however, these genomes differ with SNPs in cardiolipin synthetase, histidine kinase yycG, teichoic acid modification genes, and other genes involved in cell surface modification. Transmission electron microscopy showed that the cell walls of both strains J4206 and SA1 were significantly thicker and more electron dense than daptomycin- and vancomycin-sensitive strain J4211. This comparative genomic study has identified unique genes as well as allelic variants in the J4206 genome that are involved in cell surface modification and thus might contribute to the acquisition of daptomycin resistance.
Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK.
Maliha
M
Rahman
Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK.|Present address: U.S. Meat Animal Research Center, Clay Center, NE.
Scott V
SV
Nguyen
Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK.
Kimberly A
KA
McCullor
Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK.
Catherine J
CJ
King
Department of Pathology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX.|Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, TX.
James H
JH
Jorgensen
Department of Pharmaceutical Sciences, The University of Oklahoma College of PharmacyOklahoma, OK William-McShan@ouhsc.edu.
W Michael
WM
McShan
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D001482:Base Composition; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D002794:Choline / Q000235:genetics / Q000378:metabolism; D004251:DNA Transposable Elements; D017576:Daptomycin / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D034366:Streptococcus anginosus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D008565:Membrane Proteins; D014640:Vancomycin; D010450:Endopeptidases; C470628:LPXTGase, Streptococcus group A; D002794:Choline; D017576:Daptomycin

Streptococcus anginosus
; cell surface modification; daptomycin resistance; genome analysis; mobile genetic elements
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