ModA phasevarions regulate adherence of non-typeable Haemophilus influenzae to the host airway in a tissue-specific manner

Adherence of non-typeable Haemophilus influenzae (NTHi) to the host airway is an essential initial step for asymptomatic colonization of the nasopharynx, as well as development of disease. NTHi relies on strict regulation of multiple adhesins for its pathogenesis. The ModA phasevarion is a bacterial regulatory system important for virulence of NTHi. However, the role of the ModA phasevarion in adherence of NTHi to the host airway is not understood well. This study addressed the role of the ModA phasevarion in the regulation of adherence of NTHi to multiple substrates of the host airway. Assessment of adherence of the modA variants of four clinical isolates of NTHi showed that ModA phasevarions regulated adherence of NTHi to mucus, middle ear epithelial cells, and vitronectin in a substrate-specific manner. The adhesins Protein E and P4 were found to contribute to the ModA-regulated adherence of NTHi to distinct substrates. A better understanding of such tissue-specific regulation of NTHi adherence by the ModA phasevarion will allow identification of virulent NTHi populations at the site of disease within the host airway and facilitate more directed development of vaccines or therapeutics.