Analysis of potential virulence genes and competence to transformation in Haemophilus influenzae biotype aegyptius associated with Brazilian Purpuric Fever

Characterisation of the phase-variable autotransporter Lav reveals a role in host cell adherence and biofilm formation in Non-TypeableHaemophilus influenzae

“…Our invasive collection also represents just a 'snap-shot' of the exact phenotypic state at a particular time point during invasive infection, i.e., when treatment is required, which is likely to be during the later stages of disease. Previous work has shown that the lav gene switches OFF over subsequent episodes of infection ( 25), but can rapidly change expression over short periods (24). As we have found it to be OFF in the majority of both carriage and invasive isolates, it is possible that selection for the OFF state is due to negative selection from immune detection/pressure.…”

“…The ubiquitous presence of Lav variants 3.1 and 3.2 in H. influenzae biogroup aegyptius isolates supports the idea that these particular variants contribute to the development of BPF, although it has previously been reported that no single factor is required for BPF (47). It has also previously been reported that las expression is highly variable during an animal model of BPF (24), with expression of…”

“…Investigation into AutB in N. meningitidis found the protein played a role in biofilm formation, and was phase-varied OFF in available genomes (21). Study of another Lav homologue, Las, in H. influenzae biogroup aegyptius, has suggested a role in inflammatory cytokine production (23), and increased expression associated with disease progression (24). The function of Lav in NTHi has not been studied in detail, although over multiple rounds of infection the lav gene was shown to phase-vary OFF (25), implying selection against Lav during chronic/recurrent infections.…”

Characterization of the Phase-Variable Autotransporter Lav Reveals a Role in Host Cell Adherence and Biofilm Formation in Nontypeable Haemophilus influenzae

“…Our invasive collection also represents just a “snapshot” of the exact phenotypic state at a particular time point during invasive infection: i.e., when treatment is required, which is likely to be during the later stages of disease. Previous work has shown that the lav gene switches OFF over subsequent episodes of infection ( 25 ), but can rapidly change expression over short periods ( 24 ). As we have found it to be OFF in the majority of both carriage and invasive isolates, it is possible that selection for the OFF state is due to negative selection from immune detection/pressure.…”

“…Investigation into AutB in Neisseria meningitidis found the protein played a role in biofilm formation and was phase-varied OFF in available genomes ( 21 ). Study of another Lav homologue, Las, in H. influenzae biogroup aegyptius , has suggested a role in inflammatory cytokine production ( 23 ) and increased expression associated with disease progression ( 24 ). The function of Lav in NTHi has not been studied in detail, although over multiple rounds of infection, the lav gene was shown to phase-vary OFF ( 25 ), implying selection against Lav during chronic/recurrent infections.…”