title: Haemophilus influenzae P4 Interacts With Extracellular Matrix Proteins Promoting Adhesion and Serum Resistance.
abstract: Interaction with the extracellular matrix (ECM) is one of the successful colonization strategies employed by nontypeable Haemophilus influenzae (NTHi). Here we identified Haemophilus lipoprotein e (P4) as a receptor for ECM proteins. Purified recombinant P4 displayed a high binding affinity for laminin (Kd = 9.26 nM) and fibronectin (Kd = 10.19 nM), but slightly less to vitronectin (Kd = 16.51 nM). A P4-deficient NTHi mutant showed a significantly decreased binding to these ECM components. Vitronectin acquisition conferred serum resistance to both P4-expressing NTHi and Escherichia coli transformants. P4-mediated bacterial adherence to pharynx, type II alveolar, and bronchial epithelial cells was mainly attributed to fibronectin. Importantly, a significantly reduced bacterial infection was observed in the middle ear of the Junbo mouse model when NTHi was devoid of P4. In conclusion, our data provide new insight into the role of P4 as an important factor for Haemophilus colonization and subsequent respiratory tract infection.
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Su
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö
authors.forename: Oindrilla
authors.initials: O
authors.lastname: Mukherjee
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department for Experimental Medical Sciences Department of Respiratory Medicine and Allergology, Lund University, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hallgren
authors.affiliation: Department for Experimental Medical Sciences.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.affiliation: Mammalian Genetics Unit, MRC Harwell, Harwell Science & Innovation Campus, Oxfordshire, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Hood
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004950:Esterases / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D006192:Haemophilus Infections / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000145:classification* / Q000502:physiology*; D007797:Laminin / Q000502:physiology; D008074:Lipoproteins / Q000502:physiology*; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D010033:Otitis Media / Q000382:microbiology; D011485:Protein Binding; D011519:Proto-Oncogenes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019096:Vitronectin / Q000502:physiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D008074:Lipoproteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D014157:Transcription Factors; D019096:Vitronectin; C098614:e(P4) lipoprotein, Haemophilus influenzae; D004950:Esterases
keywords: Haemophilus influenzae; adhesion; epithelial cells; extracellular matrix; fibronectin; laminin; serum resistance; vitronectin