Phase Variation in HMW1A Controls a Phenotypic Switch in Haemophilus influenzae Associated with Pathoadaptation during Persistent Infection

Abstract

Human-adapted bacterial pathogens have evolved specific mechanisms to colonize their host niche. Phase variation is a contingency strategy to allow adaptation to changing conditions, as phase-variable bacterial loci rapidly and reversibly switch their expression.

Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2

“…7B ). These results indicated that NTHi regulates biofilm formation during persistence in COPD airways and that biofilm formation is generally inversely related to HMW1 expression, consistent with the recent observations of Fernández-Calvet et al ( 24 ).…”

“…HMW1A and 2A undergo phase variation controlled by 7-bp repeats in the promoter region upstream of the structural hmw1A and hmw2A genes ( 23 , 24 ). Given that the ~400-kb inversion occurs at the site of the HMW operons, we assessed the relationships of HMW expression with inversions and 7-bp upstream repeats.…”

Interrogation of Essentiality in the Reconstructed Haemophilus influenzae Metabolic Network Identifies Lipid Metabolism Antimicrobial Targets: Preclinical Evaluation of a FabH β-Ketoacyl-ACP Synthase Inhibitor

“…However, H. influenzae strains show high genomic and phenotypic diversity ( 3 , 44 ). To anticipate the potential role of FabHi as a broad inhibitor of H. influenzae , we examined the sequence variability of the fabH locus across a well-characterized genome-sequenced set of strains collected from COPD sputum samples over time, grouped in clonal types (CTs) ( 45 , 46 ). Being present in all strains, best hits to fabH were extracted, followed by translation and multiple alignments.…”

Biofilm aggregates and the host airway-microbial interface

“…Interestingly, the acquisition of new NTHi strains may play a role in pathogenesis ( Sethi and Murphy, 2008 ). As in chronic OM, NTHi exhibits pathoadaptation, including expressing adhesins that mediate adherence to host cells, invasion of epithelial cells, evasion of host immune cells and clearance, biofilm formation, and surface antigenic variation ( Ahearn et al., 2017 ; Fernández-Calvet et al., 2021 ).…”