title: Expression of high-level methicillin resistance in Staphylococcus aureus from the Staphylococcus sciuri mec A homologue: role of mutation(s) in the genetic background and in the coding region of mec A.
abstract: A close homologue of the mec A gene, the primary drug resistance determinant in methicillin resistant Staphylococcus aureus (MRSA), is ubiquitous in the animal commensal species Staphylococcus sciuri, yet most isolates of this staphylococcal species are susceptible to beta-lactam antibiotics including methicillin. Recently, we showed that in a methicillin-resistant mutant of S. sciuri prepared in the laboratory, the mec A homologue is converted to an antibiotic resistance gene by a point mutation introduced into the -10 consensus of the promoter and such promoter-up mutants of the S. sciuri mec A can express a significant degree of methicillin resistance when introduced into an antibiotic-susceptible strain of S. aureus. We now demonstrate that in this system further increase of the drug resistance phenotype may be achieved under antibiotic pressure by at least two different mechanisms. The first one of these involves the introduction of a point mutation at nucleotide Nt 1889 in the coding region of the S. sciuri-derived mec A determinant, resulting in the replacement of an asparagine with a threonine residue downstream of the conserved SXXK motif which causes extensive reduction in the beta-lactam antibiotic binding capacity (affinity) of the penicillin binding protein (PBP) encoded by the S. sciuri mec A homologue. A second, distinct, mechanism causing increased methicillin resistance is associated with mutation(s) of unknown nature in the genetic background of the S. aureus host.
authors.affiliation: Laboratory of Microbiology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Shang Wei
authors.initials: SW
authors.lastname: Wu
authors.forename: Herminia
authors.initials: H
authors.lastname: de Lencastre
authors.forename: Alexander
authors.initials: A
authors.lastname: Tomasz
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D016106:Methicillin Resistance / Q000235:genetics*; D010957:Plasmids; D013210:Staphylococcus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins