title: Diverse mutations in the ftsI gene in ampicillin-resistant Haemophilus influenzae isolates from pediatric patients with acute otitis media.
abstract: To clarify molecular changes in beta-lactamase-nonproducing, ampicillin-resistant (BLNAR) Haemophilus influenzae, which is increasing in pediatric patients with acute otitis media (AOM) in Japan, we identified amino acid (aa) substitutions in penicillin-binding protein 3 for the BLNAR strains. Of 191 H. influenzae strains isolated from middle ear fluid of pediatric AOM patients between October 2005 and March 2008, BLNAR strains determined by PCR accounted for 49.2%. Of the BLNAR strains, 91.5% possessed 4 aa substitutions: Met377Ile, Ser385Thr, Leu389Phe, and either Asn526Lys or Arg517His. Additionally, the emergence of BLNAR strains possessing a new aa substitution of Val329Ala in the conserved aa motif of Ser327-Thr-Val-Lys, or Val511Ala adjacent to the conserved aa motif of Lys512-Thr-Gly, was noted. Transformation of the ftsI gene into the Rd reference strain (ATCC 51907) demonstrated that these two aa substitutions reduced susceptibility to amoxicillin more than to cephalosporins. Pulsed-field gel electrophoretic profiles of BLNAR strains were highly diverse. These results suggested that inadequate antibiotic use may increase BLNAR strains by selecting mutations in the ftsI gene and that such use may have favored the new aa substitutions.
authors.affiliation: Laboratory of Molecular Epidemiology for Infectious Agents, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Kishii
authors.forename: Naoko
authors.initials: N
authors.lastname: Chiba
authors.forename: Miyuki
authors.initials: M
authors.lastname: Morozumi
authors.forename: Keiko
authors.initials: K
authors.lastname: Hamano-Hasegawa
authors.forename: Iku
authors.initials: I
authors.lastname: Kurokawa
authors.forename: Junko
authors.initials: J
authors.lastname: Masaki
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ubukata
mesh_terms: D000208:Acute Disease; D019943:Amino Acid Substitution; D000667:Ampicillin / Q000494:pharmacology*; D000668:Ampicillin Resistance / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D016521:Electrophoresis, Gel, Pulsed-Field; D006192:Haemophilus Infections / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010033:Otitis Media / Q000382:microbiology; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D046928:Peptidoglycan Glycosyltransferase / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D000667:Ampicillin; D046928:Peptidoglycan Glycosyltransferase; D014633:Valine