Nontypeable Haemophilus influenzae strains with the capsule‐associated insertion element IS1016 may mimic encapsulated strains

Abstract

With the elimination of Haemophilus influenzae type b through vaccination, it has been suggested that other types of H. influenzae strains might acquire virulence traits and emerge as important pathogens. The gene sequence IS1016 has been associated with an increased capacity to cause severe infections. It is usually present in encapsulated strains but is sometimes harbored by nontypeable H. influenzae strains. To explore this further, 118 H. influenzae isolates, collected from both patients and healthy carriers, were investigated with PCR with reference to this gene sequence. Isolates positive for the insertion element were bio- and serotyped. The presence of hmw genes for adherence, the genetic profile, and the ability to form biofilm in vitro were investigated. A total of 15 isolates were IS1016-positive, whereof 12 were nontypeable. All 12 nontypeable isolates were obtained from healthy carriers, and 92% of the isolates were biotype I. They cross-reacted to some extent with type-specific antisera or exhibited a restricted genetic diversity like encapsulated strains. Furthermore, they lacked hmw-genes, and their ability to form biofilms was comparable with a capsule-deficient type b strain. Although this subset of strains mimicked traits usually exhibited by encapsulated strains, the isolation frequency did not seem to have been affected by vaccination.

Characterisation of invasive clinicalHaemophilus influenzaeisolates in Queensland, Australia using whole-genome sequencing

“…This isolate also possessed hia and was absent for hmw genes, similar to other IS1016-positive invasive NTHi from previous studies [29,31]. IS1016 has been linked with the capacity to cause severe infections [32] and Satola et al [31] also observed a statistically significant association between younger age and the presence of IS1016 in invasive NTHi. Hi26 was isolated from a 3-year-old patient.…”

Lineage-specific Virulence Determinants ofHaemophilus influenzaeBiogroup aegyptius

“…In F3031, HIBPF06250 is interposed between tabA1 and IS 1016 (Figure 7), and the gene (like the insertion sequence) is absent in F3047. Association of IS 1016 , first described as the Haemophilus capsulation locus–associated insertion sequence, with unusual and invasive virulence of NTHI strains has been suggested elsewhere ( 17 , 18 ), although no specific gene association has been identified.…”

“…Various other BPF-specific outer membrane proteins potentially involved in host–pathogen interactions have been identified, including a partially characterized hemagglutinin ( 14 ) and an ≈145-kDa phase-variable protein eliciting protective immunity ( 15 ), but none have been fully characterized, and their role in disease has not been established. Hae BPF (but not other Hae strains) has a copy of the Haemophilus insertion element IS 1016 ( 16 ), which has been implicated in acquisition of capsulation genes and other unspecified virulence factors in other H. influenzae strains ( 17 , 18 ), but its role has not been defined.…”

Association of IS 1016 with the hia Adhesin Gene and Biotypes V and I in Invasive Nontypeable Haemophilus influenzae

“…An appreciable number of NTHI isolates show partial hybridization with cap locus sequences, most notably cap-associated IS1016, suggesting a relationship to encapsulated ancestors (36,53,60). Residual IS1016 sequence was found in a highly virulent NTHI strain, R2866 (INT1) (http://www.ncbi .nlm.nih.gov/genomes/lproks.cgi) isolated from a child with meningitis (20,21,46).…”