Characterization of the Phase-Variable Autotransporter Lav Reveals a Role in Host Cell Adherence and Biofilm Formation in Nontypeable Haemophilus influenzae
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Garai, Preeti
Tram, Greg
Martin, Gael
Van Den Bergh, Annelies
Husna, Asma-Ul
Staples, Megan
Grimwood, Keith
Jennison, Amy V
Guillon, Patrice
von Itzstein, Mark
Jennings, Michael P
Brockman, Kenneth L
Atack, John M
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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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Infection and Immunity
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© 2022 Phillips et al. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Immunology
Microbiology
Medical microbiology
Haemophilus
Lav
adherence
autotransporter
autotransporter proteins
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Phillips, ZN; Garai, P; Tram, G; Martin, G; Van Den Bergh, A; Husna, A-U; Staples, M; Grimwood, K; Jennison, AV; Guillon, P; von Itzstein, M; Jennings, MP; Brockman, KL; Atack, JM, Characterization of the Phase-Variable Autotransporter Lav Reveals a Role in Host Cell Adherence and Biofilm Formation in Nontypeable Haemophilus influenzae, Infection and Immunity, 2022, pp. e0056521