title: Inactivation of the Ecs ABC transporter of Staphylococcus aureus attenuates virulence by altering composition and function of bacterial wall.
abstract: BACKGROUND
  Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s) transported by Ecs is (are) still unknown.
  
  
  RESULTS
  In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine.
  
  
  CONCLUSIONS
  Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Göteborg, Sweden.
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Jarmo T
authors.initials: JT
authors.lastname: Juuti
authors.forename: Patrice
authors.initials: P
authors.lastname: François
authors.forename: Rana
authors.initials: R
authors.lastname: AlMajidi
authors.forename: Milla
authors.initials: M
authors.lastname: Pietiäinen
authors.forename: Myriam
authors.initials: M
authors.lastname: Girard
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Manfred J
authors.initials: MJ
authors.lastname: Saller
authors.forename: Arnold J M
authors.initials: AJ
authors.lastname: Driessen
authors.forename: Pentti
authors.initials: P
authors.lastname: Kuusela
authors.forename: Maria
authors.initials: M
authors.lastname: Bokarewa
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Vesa P
authors.initials: VP
authors.lastname: Kontinen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001329:Autolysis; D053119:Benzophenanthridines / Q000494:pharmacology; D001692:Biological Transport; D002473:Cell Wall / Q000378:metabolism*; D005260:Female; D007438:Introns; D007546:Isoquinolines / Q000494:pharmacology; D008248:Lysostaphin / Q000378:metabolism; D051379:Mice; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012270:Ribosomes / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; C016299:chelerythrine; D008248:Lysostaphin