Comparative Analyses of the Lipooligosaccharides from Nontypeable Haemophilus influenzae and Haemophilus haemolyticus Show Differences in Sialic Acid and Phosphorylcholine Modifications

Deborah M B Post; Margaret R Ketterer; Jeremy E Coffin; Lorri M Reinders; Robert S Munson Jr; Thomas Bair; Timothy F Murphy; Eric D Foster; Bradford W Gibson; Michael A Apicella

doi:10.1128/IAI.01185-15

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Comparative Analyses of the Lipooligosaccharides from Nontypeable Haemophilus influenzae and Haemophilus haemolyticus Show Differences in Sialic Acid and Phosphorylcholine Modifications

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Comparative Analyses of the Lipooligosaccharides from Nontypeable Haemophilus influenzae and Haemophilus haemolyticus Show Differences in Sialic Acid and Phosphorylcholine Modifications

Deborah M B Post, Margaret R Ketterer, Jeremy E Coffin, Lorri M Reinders, Robert S Munson Jr, Thomas Bair, Timothy F Murphy, Eric D Foster, Bradford W Gibson and Michael A Apicella

Infection and immunity, Vol.84(3), pp.765-774

01/04/2016

DOI: 10.1128/IAI.01185-15

PMCID: PMC4771351

PMID: 26729761

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Abstract

Haemophilus haemolyticus and nontypeable Haemophilus influenzae (NTHi) are closely related upper airway commensal bacteria that are difficult to distinguish phenotypically. NTHi causes upper and lower airway tract infections in individuals with compromised airways, while H. haemolyticus rarely causes such infections. The lipooligosaccharide (LOS) is an outer membrane component of both species and plays a role in NTHi pathogenesis. In this study, comparative analyses of the LOS structures and corresponding biosynthesis genes were performed. Mass spectrometric and immunochemical analyses showed that NTHi LOS contained terminal sialic acid more frequently and to a higher extent than H. haemolyticus LOS did. Genomic analyses of 10 strains demonstrated that H. haemolyticus lacked the sialyltransferase genes lic3A and lic3B (9/10) and siaA (10/10), but all strains contained the sialic acid uptake genes siaP and siaT (10/10). However, isothermal titration calorimetry analyses of SiaP from two H. haemolyticus strains showed a 3.4- to 7.3-fold lower affinity for sialic acid compared to that of NTHi SiaP. Additionally, mass spectrometric and immunochemical analyses showed that the LOS from H. haemolyticus contained phosphorylcholine (ChoP) less frequently than the LOS from NTHi strains. These differences observed in the levels of sialic acid and ChoP incorporation in the LOS structures from H. haemolyticus and NTHi may explain some of the differences in their propensities to cause disease.

Mass Spectrometry

Bacterial Proteins - genetics

Bacterial Proteins - metabolism

Haemophilus - chemistry

Haemophilus - classification

Haemophilus - isolation & purification

Haemophilus - metabolism

Haemophilus Infections - microbiology

Haemophilus influenzae - chemistry

Haemophilus influenzae - classification

Haemophilus influenzae - isolation & purification

Haemophilus influenzae - metabolism

Humans

Lipopolysaccharides - chemistry

Lipopolysaccharides - metabolism

N-Acetylneuraminic Acid - analysis

N-Acetylneuraminic Acid - metabolism

Phosphorylcholine - analysis

Phosphorylcholine - metabolism

Details

Title: Subtitle: Comparative Analyses of the Lipooligosaccharides from Nontypeable Haemophilus influenzae and Haemophilus haemolyticus Show Differences in Sialic Acid and Phosphorylcholine Modifications
Creators: Deborah M B Post - Buck Institute for Research on Aging
Margaret R Ketterer - University of Iowa
Jeremy E Coffin - University of Iowa
Lorri M Reinders - Buck Institute for Research on Aging
Robert S Munson Jr - The Ohio State University
Thomas Bair - University of Iowa
Timothy F Murphy - University at Buffalo, State University of New York
Eric D Foster - University of Iowa
Bradford W Gibson - University of California, San Francisco
Michael A Apicella - University of Iowa
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.84(3), pp.765-774
DOI: 10.1128/IAI.01185-15
PMID: 26729761
PMCID: PMC4771351
NLM abbreviation: Infect Immun
ISSN: 0019-9567
eISSN: 1098-5522
Grant note: UL1 TR001412 / NCATS NIH HHS R01 AI19641 / NIAID NIH HHS R01 AI019641 / NIAID NIH HHS R01 AI024616 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 01/04/2016
Academic Unit: Microbiology and Immunology; Biostatistics
Record Identifier: 9984364395102771

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