Mutant ftsI Genes in the Emergence of Penicillin-Binding Protein-Mediated Beta-Lactam Resistance in Haemophilus Influenzae in Norway

Clin Microbiol Infect. 2010 Aug;16(8):1117-24. doi: 10.1111/j.1469-0691.2009.03052.x. Epub 2009 Sep 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution / genetics
  • Bacterial Proteins / genetics*
  • Child
  • Child, Preschool
  • Cluster Analysis
  • DNA Fingerprinting
  • Electrophoresis, Gel, Pulsed-Field
  • Female
  • Genotype
  • Haemophilus Infections / microbiology
  • Haemophilus influenzae / classification
  • Haemophilus influenzae / enzymology*
  • Haemophilus influenzae / genetics*
  • Haemophilus influenzae / isolation & purification
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Norway
  • Penicillin-Binding Proteins / genetics*
  • Respiratory Tract Infections / microbiology
  • Sequence Analysis, DNA
  • Young Adult
  • beta-Lactam Resistance*

Substances

  • Bacterial Proteins
  • Penicillin-Binding Proteins

Associated data

  • GENBANK/FM161990
  • GENBANK/FM163633
  • GENBANK/FM163634
  • GENBANK/FM163635
  • GENBANK/FM163636
  • GENBANK/FM163637
  • GENBANK/FM163638
  • GENBANK/FM163639
  • GENBANK/FM163640
  • GENBANK/FM163641
  • GENBANK/FM163642
  • GENBANK/FM163643
  • GENBANK/FM163644
  • GENBANK/FM163645
  • GENBANK/FM163646
  • GENBANK/FM163647
  • GENBANK/FM163648
  • GENBANK/FM163649
  • GENBANK/FM163650
  • GENBANK/FM163651
  • GENBANK/FM163652
  • GENBANK/FM163653
  • GENBANK/FM163654
  • GENBANK/FM163655
  • GENBANK/FM163656
  • GENBANK/FM163657
  • GENBANK/FM163658
  • GENBANK/FM163659
  • GENBANK/FM163660
  • GENBANK/FM163661
  • GENBANK/FM163662
  • GENBANK/FM163663
  • GENBANK/FM163664
  • GENBANK/FM163665
  • GENBANK/FM163666
  • GENBANK/FM163667
  • GENBANK/FM163668
  • GENBANK/FM163669
  • GENBANK/FM163670
  • GENBANK/FM163671
  • GENBANK/FM163672
  • GENBANK/FM163673
  • GENBANK/FM163674
  • GENBANK/FM163675
  • GENBANK/FM163676
  • GENBANK/FM163677
  • GENBANK/FM163678
  • GENBANK/FM163679