Horizontal Gene Transfer of ftsI , Encoding Penicillin-Binding Protein 3, in Haemophilus influenzae

Horizontal gene transfer has been identified in only a small number of genes inHaemophilus influenzae , an organism which is naturally competent for transformation. This report provides evidence for the genetic transfer of theftsI gene, which encodes penicillin-binding protein 3, inH. influenzae . Mosaic structures of theftsI gene were found in several clinical isolates ofH. influenzae . To identify the origin of the mosaic sequence, complete sequences of the corresponding gene from seven type strains ofHaemophilus species were determined. Comparison of these sequences with mosaic regions identified a homologous recombination of theftsI gene betweenH. influenzae andHaemophilus haemolyticus . Subsequently, ampicillin-resistantH. influenzae strains harboring identicalftsI sequences were genotyped by pulsed-field gel electrophoresis (PFGE). Divergent PFGE patterns among β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains from different hospitals indicated the potential for the genetic transfer of the mutatedftsI gene between these isolates. Moreover, transfer of theftsI gene from BLNAR strains to β-lactamase-nonproducing ampicillin-susceptible (BLNAS)H. influenzae strains was evaluated in vitro. Coincubation of a BLNAS strain (a rifampin-resistant mutant of strain Rd) and BLNAR strains resulted in the emergence of rifampin- and cefdinir-resistant clones at frequencies of 5.1 × 10−7 to 1.5 × 10−6 . Characterization of these doubly resistant mutants by DNA sequencing of theftsI gene, susceptibility testing, and genotyping by PFGE revealed that theftsI genes of BLNAR strains had transferred to BLNAS strains during coincubation. In conclusion, horizontal transfer of theftsI gene inH. influenzae can occur in an intraspecies and an interspecies manner.