hicap:in silicoserotyping of theHaemophilus influenzaecapsule locus

Abstract

AbstractHaemophilus influenzaeexclusively colonises the human nasopharynx and can cause a variety of respiratory infections as well as invasive diseases including meningitis and sepsis. A key virulence determinant ofH. influenzaeis the polysaccharide capsule of which six serotypes are known, each encoded by a distinct variation of the capsule biosynthesis locus (cap-a tocap-f).H. influenzaetype b (Hib) was historically responsible for the majority of invasiveH. influenzaedisease and prevalence has been markedly reduced in countries that have implemented vaccination programs targeting this serotype. In the postvaccine era, non-typeableH. influenzaeemerged as the most dominant group causing disease but in recent years a resurgence of encapsulatedH. influenzaestrains has also been observed, most notably serotype a. Given the increasing incidence of encapsulated strains and the high frequency of Hib in countries without vaccination programs, there is growing interest in genomic epidemiology ofH. influenzae. Here we present hicap, a software tool for rapid in silico serotype prediction fromH. influenzaegenome sequences. hicap is written using Python3 and is freely available at github.com/scwatts/hicap under a GPLv3 license. To demonstrate the utility of hicap, we used it to investigate the cap locus diversity and distribution in 691 high-qualityH. influenzaegenomes from GenBank. These analyses identifiedcaploci in 95 genomes and confirmed the general association of each serotype with a unique clonal lineage and also identified occasional recombination between lineages giving rise to hybridcaploci (2% of encapsulated strains).