The Haemophilus influenzae capsulation gene cluster: a compound transposon

Abstract

The population of capsulate Haemophilus influenzae is divided into two phylogenetic divisions. Here we show that in division I strains the capsulation (cap) gene cluster lies between direct repeats of a novel insertion sequence (IS)-like element, IS1016. cap has apparently been mobilized in the chromosome as a compound transposon by IS1016, and the repeats have provided a molecular substrate for reversible cap gene amplification, with augmentation of capsule production, through unequal homologous recombination. Such amplification has occurred in serotype b strains, but in these a large direct repeat of cap genes has become fixed in the population. We have found a 1.2 kb deletion at one end of this duplicated capb locus, removing most of one copy of the polysaccharide export gene bexA. We have shown that this makes capsulation dependent on preservation of the direct repeat structure in order to avoid recombination-mediated loss of the other copy of bexA. Type b strains with this cap configuration are disseminated worldwide and currently cause nearly all invasive Haemophilus infections, leading us to speculate that the 1.2 kb deletion occurred in an ancestral type b strain and conferred significant biological advantage.

Invasive Serotype a Haemophilus influenzaeInfections With a Virulence Genotype Resembling Haemophilus influenzae Type b: Emerging Pathogen in the Vaccine Era?

“…16 In most division I isolates of Hib, the genes that are responsible for capsule synthesis and secretion, the Cap locus, are partially duplicated, with each segment flanked by the insertion element IS1016. 17 The majority of virulent Hib strains have an 1198-bp terminal deletion in 1 duplicated segment that removes a portion of IS1016 and bexA. This deletion promotes gene amplification, resulting in a dramatic increase in capsule production that is likely to contribute to the virulence of these strains.…”

Use of bexB To Detect the Capsule Locus in Haemophilus influenzae

“…1B). The genes contained within regions I and III, designated bexDCBA and hcsAB, respectively, are highly conserved across all capsular types and are required for transport of capsule constituents across the outer membrane (20,21,23,37,40). Region II genes encode capsule type a-through f-specific proteins and thus vary by serotype.…”

Copper-zinc superoxide dismutase of Haemophilus influenzae and H. parainfluenzae

“…Now this is possible for Haemophilus species, and on this score, the finding that capsulate H. influenzae strains of phylogenetic division I, important causes of invasive infections, do not carry sodC at all and that while division II strains do, they do not seem to make active enzyme, argues against the likelihood that [Cu,Zn]-SOD is critical for invasiveness. Examination of the organization of their capsulation loci suggests that division II H. influenzae type b strains are phylogenetically older than division I strains (26) and that the gene encoding inactive [Cu,Zn]-SOD is a relic of a noncapsulate ancestral strain in the former, finally eliminated from the chromosome in the latter. The finding on the other hand that sodC encodes active enzyme in common oropharyngeal and respiratory commensals suggests a possible function other than facilitating tissue invasion.…”

“…So also did type e strains, only distantly related to strains in either of the main phylogenetic divisions. DNA downstream of sodC in NCTC8468 has previously been shown to be present in strains from both phylogenetic divisions, and the DNA containing the region within which sodC would be expected to lie has been cloned from a division I type b strain (26). This cloned DNA was examined by low-stringency hybridization to pJSK114 and by sequencing to rule out the possibility that extensive sequence changes were responsible for the failure of pJSK114 to hybridize to the chromosome of division I strains, but no sodC gene was found (data not shown).…”