The disparity in diversity between unencapsulated (non-typable; NT) and encapsulated, serotypable Haemophilus influenzae (Hi) has been recognized for some time. It has previously been suggested that the wider diversity evidenced within NTHi compared with typable lineages may be due to different rates of recombination within the encapsulated and NT populations. To examine whether there is evidence for different levels of recombination within typable and NT lineages of Hi, we performed a statistical genetic analysis of 819 distinct genotypes of Hi to explore the congruence of serotype with population genetic clustering, and to identify patterns of recombination within the Hi population. We find that a significantly larger proportion of NT isolates show evidence of recombination, compared with typable isolates, and also that when admixture is present, the total amount of recombination per strain is greater within NT isolates, compared with the typable population. Furthermore, we demonstrate significant heterogeneity in the number of admixed individuals between NT lineages themselves, while such variation was not observed in typable lineages. This variability suggests that factors other than the presence of capsule are important determinants of recombination rate in the Hi population.
INTRODUCTIONHaemophilus influenzae (Hi) is a Gram-negative bacterium commonly isolated from episodes of asymptomatic nasopharyngeal carriage. While the vast majority of Hi exists in carriage rather than disease states, it remains a globally significant pathogen, capable of causing both localized mucosal infections, such as otitis media, and invasive infections, such as meningitis and septicaemia (Turk, 1984). Hi is thought to cause at least three million cases of serious illness every year, mostly in young children (WHO, 2005). To date, six distinct serotypes (designated a-f) of Hi are distinguishable (Pittman, 1930), while a substantial proportion of the population is unencapsulated and so remains non-typable (NT). Of the encapsulated population, serotype b has historically been the most significant pathogen, and is responsible for approximately 95 % of all invasive Hi disease in unvaccinated children (Falla et al., 1993;Peltola, 2000). An effective vaccine against H. influenzae serotype b (Hib) disease has been available since the early 1980s (Anderson, 1983;Chu et al., 1983), and its introduction into childhood immunization programs in the developed world has all but eliminated Hib disease in western countries (for example, see Bisgard et al., 1998;Booy et al., 1997). However, vaccination is rare in many developing countries, where Hib remains a significant cause of mortality, causing an estimated 380 000 deaths each year (WHO, 2005).While Hib disease is controlled by vaccination in the developed world, Hi possessing the other serotypes, as well as NTHi, are also reported to be capable of causing invasive disease (St Geme, 1993;Tsang et al., 2007; WaggonerFountain et al., 1995). NTHi is also a leading cause of economically signific...