AAC Accepts, published online ahead of print on 26 February 2007

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01545-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

Sho Takahata^*, Takashi Ida, Nami Senju, Yumiko Sanbongi, Aiko Miyata, Kazunori Maebashi, and Shigeru Hoshiko

Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan

^* To whom correspondence should be addressed. Email: sho_takahata{at}meiji.co.jp.

Horizontal gene transfer has been identified in only a small number of genes in Haemophilus influenzae, an organism which is naturally competent for transformation. This report provides evidence for genetic transfer of the ftsI gene, which encodes for penicillin-binding protein 3, in H. influenzae. Mosaic structures of the ftsI gene were found in several clinical isolates of H. influenzae. To identify the origin of the mosaic sequence, complete sequences of the corresponding gene from seven type strains of Haemophilus species were determined. Comparison of these sequences with mosaic regions identified a homologous recombination of the ftsI gene between H. influenzae and Haemophilus haemolyticus. Subsequently, ampicillin-resistant H. influenzae strains harboring identical ftsI sequences were genotyped by pulsed-field gel electrophoresis (PFGE). Divergent PFGE patterns among -lactamase non-producing ampicillin-resistant (BLNAR) strains from different hospitals indicated the potential of genetic transfer of the mutated ftsI gene between these isolates. Moreover, transfer of the ftsI gene from BLNAR to -lactamase non-producing ampicillin-susceptible (BLNAS) H. influenzae was evaluated in vitro. Co-incubation of BLNAS (rifampin-resistant mutant of Rd) and BLNAR strains resulted in the emergence of rifampin- and cefdinir-resistant clones at a frequency of 5.1 x 10^-7 to 1.5 x 10^-6. Characterization of these doubly resistant mutants by DNA sequencing of the ftsI gene, susceptibility testing, and genotyping using PFGE revealed that the ftsI genes of BLNAR strains had transferred to BLNAS during co-incubation. In conclusion, horizontal gene transfer of the ftsI gene in H. influenzae can occur in an intra- and inter-species manner.

This article has been cited by other articles:

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• Tristram, S. G., Pitout, M. J., Forward, K., Campbell, S., Nichols, S., Davidson, R. J. (2008). Characterization of extended-spectrum {beta}-lactamase-producing isolates of Haemophilus parainfluenzae. J Antimicrob Chemother 61: 509-514 [Abstract] [Full Text]