Haemophilus haemolyticus as a potential reservoir for ftsI gene mutations and altered penicillin-binding protein 3 mediated resistance in Haemophilus influenzae

B-lactamase-negative ampicillin-resistant (BLNAR) strains of H. influenzae are being increasingly recognised. BLNAR strains are characterized by specific ftsI gene mutations and associated amino acid substitutions in the encoded penicillin binding protein 3 (PBP3). The N526K (BLNAR defining) PBP3 substitution occurs in almost all BLNAR strains and resistance is enhanced by further substitutions (BLNAR associated) at other sites. It is generally accepted that most BLNAR strains emerge from de novo ftsI mutations in previously susceptible strains although there is some evidence of inter-strain horizontal transfer of mutated ftsI genes. Significantly, there has been one report of horizontal transfer of the ftsI gene from the respiratory commensal H. haemolyticus to H. influenzae. A role was proposed for H. haemolyticus as a reservoir of ftsI genes to mediate BLNAR type resistance in H. influenzae through recombination and formation of mosaic ftsI genes. Little is known about the frequency, nature or effect on susceptibility of ftsI mutations in H. haemolyticus and the aims of this study are to investigate this.