Table 2.

Summary of Key NTHi Surface Modifications.

Surface Component Modification	Function	Experimental Effects	Citation
Sialyation	Sialytransferases modify the LOS with environmentally available sialic acid.	Sialyated LOS glycoforms have increased biofilm formation and persistence in the rat lung model system in-vivo. NTHi grown in sialic acid deficient conditions and siaB (CMO-sialic acid synthetase) have reduced biofilm formation.	(Swords et al., 2004)
		NTHi increase LOS sialyation during planktonic to biofilm transition which promotes aggregation and further sialyation.	(Greiner et al., 2004)
Phosphorycholine (ChoP)	A hydrophilic fatty-acid that promotes initial attachment and reduces immune response to infection.	Increased ChoP glycoforms reduces LOS endotoxin bioactivity, reducing host innate response stimulation and evasion of the immune system.	(Swords et al., 2004; West-Barnette et al., 2006)
Type IV Pilus (TfP)	Filamentous structure, 6-7nm in diameter common across many bacteria cell surfaces.	Immunofluorescent studies have revealed that TfP binds to human bronchial epithelia ICAM-1 receptor facilitating non-reversible attachment.	(Novotny and Bakaletz, 2013)
	In NTHi, encoded by PilA and transported to the cell membrane by ComE secretin in NTHi, contributing to biofilm formation.	In otitis media models, TfP was visualised to be part of the integral structure of the ds-eDNA component of the EPS matrix, constituting a function in further stability.	(Jurcisek and Bakaletz, 2007)
	Initial attachment by breaking through the substratum’s repulsive forces and forming weak but attractive van der Waals forces.	TfP machinery facilitates eDNA and DNABII trafficking and release into EPS matrix, via ComE pore where TfP is expressed.	(Jurcisek et al., 2017)
OMP P5/P1	A fimbrial structure that binds to mucin, a constituent of mucus. Chronic bronchitis mucus hypersecretion provides ideal nutrient-rich substrate to bind.	OMP P5 facilitates NTHi adherence to human tracheobronchial mucin and lactoferrins, promoting biofilm formation in the human lung.	(Kubiet and Ramphal, 1995; Novotny and Bakaletz, 2013)
		16S rRNA sequencing revealed Streptococcus pneumoniae was a dominant lung taxa during AECOPD.	(Jurcisek and Bakaletz, 2007)
		A recent study has reported OMP P1 as the genuine e CEACAM-binding invasin of H. influenzae leading to attachment and internalization in the absence of OMP P5 expression.	(Tchoupa et al., 2015)
HMW1/2 adhesins	Support direct adhesion to the upper respiratory tract	Present in 80% of clinical NTHi isolates however the expression varies.	(Giufre et al., 2008)