1.
Singh, Birendra, et al.
(författare)
A fine-tuned interaction between the trimeric autotransporter Haemophilus surface fibrils and vitronectin leads to serum resistance and adherence to respiratory epithelial cells.
2014
Ingår i: Infection and Immunity. - 1098-5522. ; 82:6, s. 2378-2389
Tidskriftsartikel (refereegranskat) abstract
Haemophilus influenzae type b (Hib) escapes the host immune system by recruitment of the complement regulator vitronectin that inhibits the formation of the membrane attack complex (MAC) by inhibiting C5b-C7 complex formation and C9 polymerization. We previously reported that Hib acquires vitronectin at the surface by using Haemophilus surface fibrils (Hsf). Here we studied in detail the interaction between Hsf and vitronectin and its role in inhibition of MAC formation and invasion of lung epithelial cells. The vitronectin-binding region of Hsf was defined at the N-terminal comprising amino acids Hsf 429-652. Moreover, the Hsf recognition site on vitronectin consisted of the C-terminal amino acids 352-374. H. influenzae was killed more rapidly in vitronectin-depleted serum when compared to normal human serum (NHS), and an increased MAC deposition was observed at the surface of an Hsf-deficient H. influenzae mutant. In parallel, Hsf-expressing E. coli selectively acquired vitronectin from serum that resulted in significant inhibition of the MAC. Moreover, when vitronectin was bound to Hsf an increased bacterial adherence and internalization of epithelial cells was observed. Taken together, we have defined a fine-tuned protein-protein interaction between Hsf and vitronectin that may contribute to an increased virulence of Hib.
2.
Su, Shanice Yc, et al.
(författare)
The Laminin Interactome : A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization
2019
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 220:6, s. 1049-1060
Tidskriftsartikel (refereegranskat) abstract
Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilusinfluenzae (NTHi) colonization in the airway mucosa. Here we identified elongation factor thermo-unstable (EF-Tu), L-lactate dehydrogenase (LDH), Protein D and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (P4, PE, PF and Hap), EF-Tu, LDH, PD and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. Importantly, the NTHi laminin interactome consisting of the well-studied and novel Lbps recognized laminin LG domains from the subunit α chains of laminin-111 and -332, of which the latter isoform is the main laminin in the airway BM. The NTHi interactome mainly targeted multiple heparin-binding domains of laminin. In conclusion, the NTHi interactome exhibited a high plasticity of interactions with different laminin isoforms via multiple heparin-binding sites.
