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

相变自转运体 Lav 的表征揭示了其在非典型流感嗜血杆菌中宿主细胞粘附和生物膜形成中的作用

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作者:Zachary N Phillips, Preeti Garai, Greg Tram, Gael Martin, Annelies Van Den Bergh, Asma-Ul Husna, Megan Staples, Keith Grimwood, Amy V Jennison, Patrice Guillon, Mark von Itzstein, Michael P Jennings, Kenneth L Brockman, John M Atack

Abstract

Lav is an autotransporter protein found in pathogenic Haemophilus and Neisseria species. Lav in nontypeable 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 human lung cells and denser biofilm formation. A survey of Haemophilus species genome sequences showed lav is present in ∼60% of NTHi strains, but lav is not present in most typeable H. influenzae strains. 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.

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