Biomaterial Database

Otitis media associated polymorphisms in the hemin receptor HemR of nontypeable Haemophilus influenzae. 2014

Nathan C LaCross, and Carl F Marrs, and Janet R Gilsdorf

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: nlacros@umich.edu.

Nontypeable Haemophilus influenzae (NTHi) colonize the human pharynx asymptomatically, and are also an important cause of otitis media (OM). Previous studies have demonstrated that some genes are more prevalent in OM-causing NTHi strains than in commensal strains, suggesting a role in virulence. These studies, however, are unable to investigate the possible associations between gene polymorphisms and disease. This study examined amino acid polymorphisms and sequence diversity in a potential virulence gene, the hemin receptor hemR, from a previously characterized NTHi strain collection containing both commensal and OM organisms to identify possible associations between the polymorphisms and otitis media. The full open reading frame of hemR was sequenced from a total of 146 NTHi isolates, yielding a total of 47 unique HemR amino acid sequences. The predicted structure of HemR showed substantial similarity to a class of monomeric TonB dependent, ligand-gated channels involved in iron acquisition in other gram negative bacteria. Fifteen amino acid polymorphisms were significantly more prevalent at the 90% confidence level among commensal compared to OM isolates. Upon controlling for the confounding effect of population structure, over half of the polymorphism-otitis media relationships lost statistical significance, emphasizing the importance of assessing the effect of population structure in association studies. The seven polymorphisms that retained significance were dispersed throughout the protein in various functional and structural domains, including the signal peptide, N-terminal plug domain, and intra- and extracellular loops. The alternate amino acid of only one of these seven polymorphisms was more common among OM isolates, demonstrating a strong trend toward the consensus sequence among disease causing NTHi. We hypothesize that variability at these positions in HemR may result in a reduced ability to acquire iron, rendering NTHi with such versions of the gene less fit for survival in the middle ear environment.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010033	Otitis Media	Inflammation of the MIDDLE EAR including the AUDITORY OSSICLES and the EUSTACHIAN TUBE.	Middle Ear Inflammation,Inflammation, Middle Ear
D011110	Polymorphism, Genetic	The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.	Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D006192	Haemophilus Infections	Infections with bacteria of the genus HAEMOPHILUS.	Hemophilus Infections,Haemophilus influenzae Infection,Haemophilus influenzae Type b Infection,Hib Infection,Infections, Haemophilus,Infections, Hemophilus,Haemophilus Infection,Haemophilus influenzae Infections,Hemophilus Infection,Hib Infections,Infection, Haemophilus,Infection, Haemophilus influenzae,Infection, Hemophilus,Infection, Hib
D006193	Haemophilus influenzae	A species of HAEMOPHILUS found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII.	Bacterium influenzae,Coccobacillus pfeifferi,Haemophilus meningitidis,Hemophilus influenzae,Influenza-bacillus,Mycobacterium influenzae
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001425	Bacterial Outer Membrane Proteins	Proteins isolated from the outer membrane of Gram-negative bacteria.	OMP Proteins,Outer Membrane Proteins, Bacterial,Outer Membrane Lipoproteins, Bacterial
D016366	Open Reading Frames	A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).	ORFs,Protein Coding Region,Small Open Reading Frame,Small Open Reading Frames,sORF,Unassigned Reading Frame,Unassigned Reading Frames,Unidentified Reading Frame,Coding Region, Protein,Frame, Unidentified Reading,ORF,Open Reading Frame,Protein Coding Regions,Reading Frame, Open,Reading Frame, Unassigned,Reading Frame, Unidentified,Region, Protein Coding,Unidentified Reading Frames