Skip to main content
Top
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Differential distribution of IgA-protease genotypes in mucosal and invasive isolates of Haemophilus influenzae in Sweden

Authors: Fredrik Resman, Guillaume Manat, Victor Lindh, Timothy F. Murphy, Kristian Riesbeck

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Several different IgA-proteases exist in Haemophilus influenzae. The variants have been suggested to play differential roles in pathogenesis, but there is limited information on their distribution in clinical isolates. The objective of this study was to investigate the distribution of IgA-protease genotypes in H. influenzae and assess the association between IgA-protease genotype and type of clinical infection.

Methods

We performed PCR-screening of the IgA-protease gene variants in two cohorts of clinical H. influenzae. The first cohort consisted of 177 isolates from individuals with respiratory tract infection in January 2010, 2011 and 2012. Information on age, gender and clinical infection was available in this cohort. The second cohort comprised 53 isolates, including NTHi from bloodstream, cerebrospinal fluid (CSF) and urogenital origin as well as encapsulated isolates respresenting all capsule types. We assessed associations between IgA protease genotype and clinical predictors using basic statistical tests of association as well as regression analysis.

Results

The igaB gene was found in 46% of isolates in the respiratory tract cohort, and no evident trend could be seen during the study years. However, the igaB gene was significantly less common among invasive isolates (19%), p = 0.003 (Fischer’s exact test), even when encapsulated isolates were excluded (21%), p = 0.012. A significantly negative association between bacteraemia and igaB genotype remained after adjusting for covariates. We did not identify a significant association between IgA-protease gene variants and type of respiratory tract infection, but isolates with an igaA2 genotype were overrepresented in pre-school children.

Conclusions

The distribution of IgA-protease gene variants in Swedish H. influenzae highlighted the widespread abundance of the igaB in isolates from cases of respiratory tract infection, but the igaB gene variant was significantly less common in invasive (bloodstream and CSF) isolates of H. influenzae compared with respiratory tract isolates.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kett K, Brandtzaeg P, Radl J, Haaijman JJ. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986;136(10):3631–5.PubMed Kett K, Brandtzaeg P, Radl J, Haaijman JJ. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986;136(10):3631–5.PubMed
2.
go back to reference Male CJ. Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae. Infect Immun. 1979;26(1):254–61.PubMedPubMedCentral Male CJ. Immunoglobulin A1 protease production by Haemophilus influenzae and Streptococcus pneumoniae. Infect Immun. 1979;26(1):254–61.PubMedPubMedCentral
3.
go back to reference Mulks MH, Plaut AG. IgA protease production as a characteristic distinguishing pathogenic from harmless neisseriaceae. N Engl J Med. 1978;299(18):973–6.CrossRef Mulks MH, Plaut AG. IgA protease production as a characteristic distinguishing pathogenic from harmless neisseriaceae. N Engl J Med. 1978;299(18):973–6.CrossRef
4.
go back to reference Kilian M, Mestecky J, Schrohenloher RE. Pathogenic species of the genus Haemophilus and Streptococcus pneumoniae produce immunoglobulin A1 protease. Infect Immun. 1979;26(1):143–9.PubMedPubMedCentral Kilian M, Mestecky J, Schrohenloher RE. Pathogenic species of the genus Haemophilus and Streptococcus pneumoniae produce immunoglobulin A1 protease. Infect Immun. 1979;26(1):143–9.PubMedPubMedCentral
5.
go back to reference Kilian M, Reinholdt J, Lomholt H, Poulsen K, Frandsen EV. Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS. 1996;104(5):321–38.CrossRef Kilian M, Reinholdt J, Lomholt H, Poulsen K, Frandsen EV. Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS. 1996;104(5):321–38.CrossRef
6.
go back to reference Kilian M, Thomsen B, Petersen TE, Bleeg H. Molecular biology of Haemophilus influenzae IgA1 proteases. Mol Immunol. 1983;20(9):1051–8.CrossRef Kilian M, Thomsen B, Petersen TE, Bleeg H. Molecular biology of Haemophilus influenzae IgA1 proteases. Mol Immunol. 1983;20(9):1051–8.CrossRef
7.
go back to reference Mulks MH, Kornfeld SJ, Frangione B, Plaut AG. Relationship between the specificity of IgA proteases and serotypes in Haemophilus influenzae. J Infect Dis. 1982;146(2):266–74.CrossRef Mulks MH, Kornfeld SJ, Frangione B, Plaut AG. Relationship between the specificity of IgA proteases and serotypes in Haemophilus influenzae. J Infect Dis. 1982;146(2):266–74.CrossRef
8.
go back to reference Kilian M, Thomsen B. Antigenic heterogeneity of immunoglobulin A1 proteases from encapsulated and non-encapsulated Haemophilus influenzae. Infect Immun. 1983;42(1):126–32.PubMedPubMedCentral Kilian M, Thomsen B. Antigenic heterogeneity of immunoglobulin A1 proteases from encapsulated and non-encapsulated Haemophilus influenzae. Infect Immun. 1983;42(1):126–32.PubMedPubMedCentral
9.
go back to reference Fernaays MM, Lesse AJ, Sethi S, Cai X, Murphy TF. Differential genome contents of nontypeable Haemophilus influenzae strains from adults with chronic obstructive pulmonary disease. Infect Immun. 2006;74(6):3366–74.CrossRef Fernaays MM, Lesse AJ, Sethi S, Cai X, Murphy TF. Differential genome contents of nontypeable Haemophilus influenzae strains from adults with chronic obstructive pulmonary disease. Infect Immun. 2006;74(6):3366–74.CrossRef
10.
go back to reference Spahich NA, St Geme JW 3rd. Structure and function of the Haemophilus influenzae autotransporters. Front Cell Infect Microbiol. 2011;1:5.CrossRef Spahich NA, St Geme JW 3rd. Structure and function of the Haemophilus influenzae autotransporters. Front Cell Infect Microbiol. 2011;1:5.CrossRef
11.
go back to reference Fernaays MM, Lesse AJ, Cai X, Murphy TF. Characterization of igaB, a second immunoglobulin A1 protease gene in nontypeable Haemophilus influenzae. Infect Immun. 2006;74(10):5860–70.CrossRef Fernaays MM, Lesse AJ, Cai X, Murphy TF. Characterization of igaB, a second immunoglobulin A1 protease gene in nontypeable Haemophilus influenzae. Infect Immun. 2006;74(10):5860–70.CrossRef
12.
go back to reference Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. Expression of IgA proteases by Haemophilus influenzae in the respiratory tract of adults with chronic obstructive pulmonary disease. J Infect Dis. 2015;212(11):1798–805.CrossRef Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. Expression of IgA proteases by Haemophilus influenzae in the respiratory tract of adults with chronic obstructive pulmonary disease. J Infect Dis. 2015;212(11):1798–805.CrossRef
13.
go back to reference Murphy TF, Kirkham C, Gallo MC, Yang Y, Wilding GE, Pettigrew MM. Immunoglobulin A protease variants facilitate intracellular survival in epithelial cells by nontypeable Haemophilus influenzae that persist in the human respiratory tract in chronic obstructive pulmonary disease. J Infect Dis. 2017;216(10):1295–302.CrossRef Murphy TF, Kirkham C, Gallo MC, Yang Y, Wilding GE, Pettigrew MM. Immunoglobulin A protease variants facilitate intracellular survival in epithelial cells by nontypeable Haemophilus influenzae that persist in the human respiratory tract in chronic obstructive pulmonary disease. J Infect Dis. 2017;216(10):1295–302.CrossRef
14.
go back to reference Clementi CF, Hakansson AP, Murphy TF. Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence. Infect Immun. 2014;82(1):433–44.CrossRef Clementi CF, Hakansson AP, Murphy TF. Internalization and trafficking of nontypeable Haemophilus influenzae in human respiratory epithelial cells and roles of IgA1 proteases for optimal invasion and persistence. Infect Immun. 2014;82(1):433–44.CrossRef
15.
go back to reference King PT, Ngui J, Gunawardena D, Holmes PW, Farmer MW, Holdsworth SR. Systemic humoral immunity to non-typeable Haemophilus influenzae. Clin Exp Immunol. 2008;153(3):376–84.CrossRef King PT, Ngui J, Gunawardena D, Holmes PW, Farmer MW, Holdsworth SR. Systemic humoral immunity to non-typeable Haemophilus influenzae. Clin Exp Immunol. 2008;153(3):376–84.CrossRef
16.
go back to reference Vitovski S, Dunkin KT, Howard AJ, Sayers JR. Nontypeable Haemophilus influenzae in carriage and disease: a difference in IgA1 protease activity levels. JAMA. 2002;287(13):1699–705.CrossRef Vitovski S, Dunkin KT, Howard AJ, Sayers JR. Nontypeable Haemophilus influenzae in carriage and disease: a difference in IgA1 protease activity levels. JAMA. 2002;287(13):1699–705.CrossRef
17.
go back to reference Lomholt H, van Alphen L, Kilian M. Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect Immun. 1993;61(11):4575–81.PubMedPubMedCentral Lomholt H, van Alphen L, Kilian M. Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect Immun. 1993;61(11):4575–81.PubMedPubMedCentral
18.
go back to reference Erwin AL, Sandstedt SA, Bonthuis PJ, Geelhood JL, Nelson KL, Unrath WC, Diggle MA, Theodore MJ, Pleatman CR, Mothershed EA, Sacchi CT, Mayer LW, Gilsdorf JR, Smith AL. Analysis of genetic relatedness of Haemophilus influenzae isolates by multilocus sequence typing. J Bacteriol. 2008;190(4):1473–83.CrossRef Erwin AL, Sandstedt SA, Bonthuis PJ, Geelhood JL, Nelson KL, Unrath WC, Diggle MA, Theodore MJ, Pleatman CR, Mothershed EA, Sacchi CT, Mayer LW, Gilsdorf JR, Smith AL. Analysis of genetic relatedness of Haemophilus influenzae isolates by multilocus sequence typing. J Bacteriol. 2008;190(4):1473–83.CrossRef
19.
go back to reference De Chiara M, Hood D, Muzzi A, Pickard DJ, Perkins T, Pizza M, Dougan G, Rappuoli R, Moxon ER, Soriani M, Donati C. Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure. Proc Natl Acad Sci U S A. 2014;111(14):5439–44.CrossRef De Chiara M, Hood D, Muzzi A, Pickard DJ, Perkins T, Pizza M, Dougan G, Rappuoli R, Moxon ER, Soriani M, Donati C. Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure. Proc Natl Acad Sci U S A. 2014;111(14):5439–44.CrossRef
20.
go back to reference Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source code for biology and medicine. 2008;3:17.CrossRef Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source code for biology and medicine. 2008;3:17.CrossRef
Metadata
Title
Differential distribution of IgA-protease genotypes in mucosal and invasive isolates of Haemophilus influenzae in Sweden
Authors
Fredrik Resman
Guillaume Manat
Victor Lindh
Timothy F. Murphy
Kristian Riesbeck
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3464-3

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.