1. Mutant ftsI genes in the emergence of penicillin-binding proteinmediated β-lactam resistance in Haemophilus influenzae in Norway
- Author
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Bjørn-Erik Kristiansen, A.-G. Allum, Yngvar Tveten, Linda Strand, Andrew Jenkins, A. Lia, I. L. Anthonisen, and D. Skaare
- Subjects
Adult ,Male ,Microbiology (medical) ,Haemophilus Infections ,Penicillin binding proteins ,Adolescent ,Genotype ,Molecular Sequence Data ,Mutation, Missense ,clonality ,Microbial Sensitivity Tests ,Gene mutation ,Biology ,medicine.disease_cause ,beta-Lactam Resistance ,Haemophilus influenzae ,Microbiology ,Young Adult ,Bacterial Proteins ,Ampicillin ,medicine ,Pulsed-field gel electrophoresis ,Cluster Analysis ,Humans ,Penicillin-Binding Proteins ,Child ,Respiratory Tract Infections ,Aged ,Antibacterial agent ,Aged, 80 and over ,Genetics ,Norway ,Infant ,Sequence Analysis, DNA ,General Medicine ,Middle Aged ,DNA Fingerprinting ,recombination ,Electrophoresis, Gel, Pulsed-Field ,Infectious Diseases ,Amino Acid Substitution ,Child, Preschool ,Female ,Penicillin binding ,BLNAR ,H. influenzae, PBP3 ,medicine.drug - Abstract
The most important mechanism for beta-lactam resistance in beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae is the alteration of penicillin-binding protein 3 (PBP3) as a result of ftsI gene mutations. The present study aimed to map PBP3 alterations and to determine the correlation to beta-lactam resistance in respiratory tract isolates of H. influenzae in Norway, as well as assess the contribution of clonal spread to the emergence of PBP3-mediated resistance. Twenty-three beta-lactamase negative respiratory tract isolates with resistance to penicillins and 23 susceptible control isolates were examined by determination of beta-lactam MICs, ftsI sequencing and molecular typing by pulsed-field gel electrophoresis (PFGE). Ampicillin MIC ranges in the resistant group and the control group were 1-2 mg/L and 0.125-0.5 mg/L, respectively. All isolates in the resistant group had the PBP3 substitution Asn526-->Lys and were thus categorized as group II low-BLNAR. No control isolate met the genetic BLNAR (gBLNAR) criteria. The PBP3 substitution patterns corresponded well to those observed in previous European studies. Eighty-three percent (19/23) of the resistant isolates belonged to two clones, demonstrating the capability of low-BLNAR strains of clonal dissemination. Combined analysis of ftsI DNA sequences and PFGE patterns revealed distinctly different ftsI alleles in genetically indistinguishable isolates and identical copies of the same ftsI allele in unrelated isolates. A possible explanation of this observation is the recombinational exchange of ftsI alleles. This phenomenon, as well as the possibility of endemic European gBLNAR strains, should be further investigated.
- Published
- 2010
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