scholarly journals The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization

2019 ◽  
Vol 220 (6) ◽  
pp. 1049-1060 ◽  
Author(s):  
Yu-Ching Su ◽  
Emma Mattsson ◽  
Birendra Singh ◽  
Farshid Jalalvand ◽  
Timothy F Murphy ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Elongation Factor ◽  
High Plasticity ◽  
Heparin Binding ◽  
Nontypeable Haemophilus Influenzae ◽  
Binding Domains ◽  
Airway Mucosa ◽  
Epithelial Cell Lines ◽  
Pulmonary Epithelial Cell ◽  
Laminin Binding

Abstract Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilus influenzae (NTHi) colonization in the airway mucosa. In this study, we identified elongation factor thermo-unstable (EF-Tu), l-lactate dehydrogenase (LDH), protein D (PD), and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (protein 4 [P4], protein E [PE], protein F [PF], and Haemophilus adhesion and penetration protein [Hap]), EF-Tu, LDH, PD, and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. More 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, the latter isoform of which 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.

scholarly journals Interaction of Fimbriae of Haemophilus influenzae Type B with Heparin-Binding Extracellular Matrix Proteins

2000 ◽  
Vol 68 (10) ◽  
pp. 5696-5701 ◽  
Author(s):  
Ritva Virkola ◽  
Mirko Brummer ◽  
Heikki Rauvala ◽  
Loek van Alphen ◽  
Timo K. Korhonen
Keyword(s):  
Extracellular Matrix ◽  
Haemophilus Influenzae ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Haemophilus Influenzae Type ◽  
Heparin Binding ◽  
Type B ◽  
Binding Domains ◽  
Human Fibronectin ◽  
High Concentrations

ABSTRACT The interaction of the fimbriae of Haemophilus influenzae type b (Hib) with two heparin-binding extracellular matrix proteins, human fibronectin (Fn) and heparin-binding growth-associated molecule (HB-GAM) from mouse, were studied. The fimbriated Hib strain 770235 fim+, as well as the recombinant strainE. coli HB101(pMH140), which expressed Hib fimbriae, adhered strongly to Fn and HB-GAM immobilized on glass. Purified Hib fimbriae bound to Fn and HB-GAM, and within the Fn molecule, the binding was localized to the N-terminal 30,000-molecular-weight (30K) and 40K fragments, which contain heparin-binding domains I and II, respectively. Fimbrial binding to Fn, HB-GAM, and the 30K and the 40K fragments was inhibited by high concentrations of heparin. The results show that fimbriae of Hib interact with heparin-binding extracellular matrix proteins. The nonfimbriated Hib strain 770235 fim− exhibited a low level of adherence to Fn but did not react with HB-GAM, indicating that Hib strains also possess a fimbria-independent mechanism to interact with Fn.

scholarly journals Conservation and Diversity of HMW1 and HMW2 Adhesin Binding Domains among Invasive Nontypeable Haemophilus influenzae Isolates

2006 ◽  
Vol 74 (2) ◽  
pp. 1161-1170 ◽  
Author(s):  
Maria Giufrè ◽  
Michele Muscillo ◽  
Patrizia Spigaglia ◽  
Rita Cardines ◽  
Paola Mastrantonio ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Structural Genes ◽  
High Similarity ◽  
Nontypeable Haemophilus Influenzae ◽  
Variable Regions ◽  
The Core ◽  
Binding Domains ◽  
Maximal Sequence ◽  
Nthi Strain ◽  
Pcr Products

ABSTRACT The pathogenesis of nontypeable Haemophilus influenzae (NTHi) begins with adhesion to the rhinopharyngeal mucosa. In almost 80% of NTHi clinical isolates, the HMW proteins are the major adhesins. The prototype HMW1 and HMW2 proteins, identified in NTHi strain 12, exhibit different binding specificities. The two binding domains have been localized in regions of maximal sequence dissimilarity (40% identity, 58% similarity). Two areas within these binding domains have been found essential for full level adhesive activity (designated the core-binding domains). To investigate the conservation and diversity of the HMW1 and HMW2 core-binding domains among isolates, PCR and DNA sequencing were used. First, we separately amplified the hmw1A-like and hmw2A-like structural genes in nine invasive NTHi isolates, discovering two new hmwA alleles, whose sequences are herein reported. Then, the hmw1A-like and hmw2A-like PCR products were used as the template in nested PCR to produce amplicons encompassing the encoding sequences of the two core-binding domains. In-depth sequence analysis was then performed among sequences of each group, with the support of specific computer programs. Overall, extensive sequence diversity among isolates was highlighted. However, similarity plots showed patterns consisting of peaks of relatively high similarity alternating with strongly divergent regions. The phylogenetic tree clearly indicated the HMW1-like and HMW2-like core-binding domain sequences as two clusters. Distinct sets of conserved amino acid motifs were identified within each group of sequences using the MEME/MOTIFSEARCH tool. Since HMW adhesins could represent candidates for future vaccines, identification of specific patterns of conserved motifs in otherwise highly variable regions is of great interest.

scholarly journals Pseudomonas aeruginosa uses multiple receptors for adherence to laminin during infection of the respiratory tract and skin wounds

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Magnus Paulsson ◽  
Yu-Ching Su ◽  
Tamara Ringwood ◽  
Fabian Uddén ◽  
Kristian Riesbeck
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Heparin Binding ◽  
Surface Receptors ◽  
Binding Domains ◽  
Laminin Receptors ◽  
Multiple Receptors ◽  
Main Component ◽  
Tract Infections

AbstractPseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat. Laminin is a main component of the extracellular matrix, and in this study we defined bacterial laminin receptors on P. aeruginosa. Persistent clinical P. aeruginosa isolates from patients with cystic fibrosis, wounds or catheter-related urinary tract infections bound more laminin compared to blood isolates. Laminin receptors in the outer membrane were revealed by 2D-immunblotting, and the specificities of interactions were confirmed with ELISA and biolayer interferometry. Four new high-affinity laminin receptors were identified in the outer membrane; EstA, OprD, OprG and PA3923. Mutated bacteria devoid of these receptors adhered poorly to immobilized laminin. All bacterial receptors bound to the heparin-binding domains on LG4 and LG5 of the laminin alpha chain as assessed with truncated laminin fragments, transmission electron microscopy and inhibition by heparin. In conclusion, P. aeruginosa binds laminin via multiple surface receptors, and isolates from lungs of cystic fibrosis patients bound significantly more laminin compared to bacteria isolated from the skin and urine. Since laminin is abundant in both the lungs and skin, we suggest that laminin binding is an important mechanism in P. aeruginosa pathogenesis.

scholarly journals Antisera Against Certain Conserved Surface-Exposed Peptides of Nontypeable Haemophilus influenzae Are Protective

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0136867 ◽  
Author(s):  
Paul W. Whitby ◽  
Thomas W. Seale ◽  
Daniel J. Morton ◽  
Terrence L. Stull
Keyword(s):  
Haemophilus Influenzae ◽  
Nontypeable Haemophilus Influenzae

Spontaneous Bacterial Peritonitis Caused by Nontypeable Haemophilus influenzae in a Previously Healthy Child

2013 ◽  
Vol 32 (6) ◽  
pp. 704
Author(s):  
Anastasia Dimopoulou ◽  
Dimitra Dimopoulou ◽  
Efstratios Christianakis ◽  
Dimitrios Bourikas ◽  
Ioannis Alexandrou ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Healthy Child ◽  
Spontaneous Bacterial Peritonitis ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Peritonitis

scholarly journals Biofilm Growth Increases Phosphorylcholine Content and Decreases Potency of Nontypeable Haemophilus influenzae Endotoxins

2006 ◽  
Vol 74 (3) ◽  
pp. 1828-1836 ◽  
Author(s):  
Shayla West-Barnette ◽  
Andrea Rockel ◽  
W. Edward Swords
Keyword(s):  
Haemophilus Influenzae ◽  
Inflammatory Responses ◽  
Opportunistic Pathogen ◽  
Host Responses ◽  
Toll Like Receptor ◽  
Nontypeable Haemophilus Influenzae ◽  
Toll Like Receptor 4 ◽  
Biofilm Growth ◽  
Bacterial Endotoxins ◽  
Cell Layers

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) is a common respiratory commensal and opportunistic pathogen. NTHI is normally contained within the airways by host innate defenses that include recognition of bacterial endotoxins by Toll-like receptor 4 (TLR4). NTHI produces lipooligosaccharide (LOS) endotoxins which lack polymeric O side chains and which may contain host glycolipids. We recently showed that NTHI biofilms contain variants with sialylated LOS glycoforms that are essential to biofilm formation. In this study, we show that NTHI forms biofilms on epithelial cell layers. Confocal analysis revealed that sialylated variants were distributed throughout the biofilm, while variants expressing phosphorylcholine (PCho) were found within the biofilm. Consistent with this observation, PCho content of LOS purified from NTHI biofilms was increased compared to LOS from planktonic cultures. Hypothesizing that the observed changes in endotoxin composition could affect bioactivity, we compared inflammatory responses to NTHI LOS purified from biofilm and planktonic cultures. Our results show that endotoxins from biofilms induced weaker host innate responses. While we observed a minimal effect of sialylation on LOS bioactivity, there was a significant decrease in bioactivity associated with PCho substitutions. We thus conclude that biofilm growth increases the proportion of PCho+ variants in an NTHI population, resulting in a net decrease in LOS bioactivity. Thus, in addition to their well-documented resistance phenotypes, our data show that biofilm communities of NTHI bacteria contain variants that evoke less potent host responses.

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