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

Abstract

Lav is an autotransporter protein found in pathogenic Haemophilus and Neisseria species. Lav in non-typeable Haemophilus influenzae (NTHi) is phase-variable: the gene reversibly switches ON-OFF via changes in length of a locus-located GCAA(n) simple DNA sequence repeat tract. The expression status of lav was examined in carriage and invasive collections of NTHi, where it was predominantly not expressed (OFF). Phenotypic study showed lav expression (ON) results in increased adherence to host cells, and denser biofilm formation. A survey of Haemophilus spp. genome sequences showed lav is present in [~]60% of NTHi strains, but lav is not present in most typeable H. influenzae. Sequence analysis revealed a total of five distinct variants of the Lav passenger domain present in Haemophilus spp., with these five variants showing a distinct lineage distribution. Determining the role of Lav in NTHi will help understand the role of this protein during distinct pathologies.