Characterization of the Phase-Variable Autotransporter Lav Reveals a Role in Host Cell Adherence and Biofilm Formation in Nontypeable Haemophilus influenzae.
Zachary N PhillipsPreeti GaraiGreg TramGael MartinAnnelies Van Den BerghAsma-Ul HusnaMegan StaplesKeith GrimwoodAmy V JennisonPatrice GuillonMark von ItzsteinMichael P JenningsKenneth L BrockmanJohn M AtackPublished in: Infection and immunity (2022)
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.
Keyphrases
- biofilm formation
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- candida albicans
- poor prognosis
- copy number
- single cell
- binding protein
- induced apoptosis
- genome wide
- cystic fibrosis
- cell cycle arrest
- cell death
- dna methylation
- long non coding rna
- adipose tissue
- mesenchymal stem cells
- cell therapy
- skeletal muscle
- transcription factor
- signaling pathway
- genome wide identification