title: Nosocomial outbreak of ceftazidime-resistant Serratia marcescens strains that produce a chromosomal AmpC variant with N235K substitution.
abstract: Serratia marcescens is a Gram-negative bacterium that is often associated with nosocomial infections. Here we analyzed the resistance mechanism of the ceftazidime-resistant S. marcescens nosocomial strains. The five S. marcescens urinary tract infection-associated isolates were positive for chromosomal ampC and bla(TEM-1). Four of the five strains, ES11, ES31, ES42, and ES46, were single clone and ceftazidime resistant. The fifth strain, ES71, was susceptible to ceftazidime. Analysis of the deduced amino acid sequence revealed a Glu-235-Lys substitution in the third amino acid of the third motif of AmpC from both ES46 and ES71, and a site-directed mutagenesis experiment confirmed that this substitution is involved in the ceftazidime resistance phenotype. However, the resistance phenotypes of strains ES46 and ES71 to ceftazidime were quite different from one another, indicating that another mechanism, in addition to the AmpC mutation, is also involved in the determination of the resistance phenotype of these strains. Basal AmpC activity was more than two times higher in strain ES46 than in ES71, which could result in the differing resistance phenotypes of these two strains. The clinical significance and prevalence of extended-spectrum cephalosporin-resistant S. marcescens strains harboring the mutated chromosomal ampC gene are unclear in Japan and remain to be elucidated.
authors.affiliation: Akita Prefectural Institute of Public Health, Sensyu kubota-machi, Akita 010-0874, Japan. jyatsu@spica.freemail.ne.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Yatsuyanagi
authors.forename: Shioko
authors.initials: S
authors.lastname: Saito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Konno
authors.forename: Seizaburo
authors.initials: S
authors.lastname: Harata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Amano
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002442:Ceftazidime / Q000494:pharmacology*; D018550:Cephalosporin Resistance / Q000235:genetics*; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology*; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field / Q000379:methods; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000379:methods; D016868:Serratia Infections / Q000453:epidemiology / Q000382:microbiology*; D012706:Serratia marcescens / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D014169:Transformation, Bacterial; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D065093:beta-Lactamase Inhibitors; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases