title: Jumping the barrier to beta-lactam resistance in Staphylococcus aureus.
abstract: Although the staphylococcal methicillin resistance determinant, mecA, resides on a mobile genetic element, staphylococcus cassette chromosome mec (SCCmec), its distribution in nature is limited to as few as five clusters of related methicillin-resistant Staphylococcus aureus (MRSA) clones. To investigate the potential role of the host chromosome in clonal restriction of the methicillin resistance determinant, we constructed plasmid pYK20, carrying intact mecA, and introduced it into several methicillin-susceptible Staphylococcus aureus strains, five of which were naive hosts (i.e., mecA not previously resident on the host chromosome) and five of which were experienced hosts (i.e., methicillin-susceptible variants of MRSA strains from which SCCmec was excised). We next assessed the effect of the recipient background on the methicillin resistance phenotype by population analysis, by assaying the mecA expression of PBP2a by Western blot analysis, and by screening for mutations affecting mecA. Each experienced host transformed with pYK20 had a resistance phenotype and expressed PBP2a similar to that of the parent with chromosomal SCCmec, but naive hosts transformed with pYK20 selected against its expression, indicative of a host barrier. Either inducible beta-lactamase regulatory genes blaR1-blaI or homologous regulatory genes mecR1-mecI, which control mecA expression, acted as compensatory elements, permitting the maintenance and expression of plasmid-carried mecA.
authors.affiliation: Division of Infectious Diseases, San Francisco General Hospital, University of California, San Francisco, California 94143-0811, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katayama
authors.forename: Hong-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Hong
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics; D002876:Chromosomes, Bacterial; D004251:DNA Transposable Elements; D022761:Gene Transfer, Horizontal; D005809:Genes, Regulator; D016106:Methicillin Resistance / Q000235:genetics; D009154:Mutation; D046915:Penicillin-Binding Proteins; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics / Q000502:physiology*; D014169:Transformation, Bacterial / Q000235:genetics; D018440:beta-Lactam Resistance / Q000235:genetics / Q000502:physiology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D046915:Penicillin-Binding Proteins; D001618:beta-Lactamases