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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):1699–1705. doi:10.1001/jama.287.13.1699
Author Affiliations: Division of Genomic Medicine, Infection and Immunity Group, Royal Hallamshire Hospital, Sheffield, England (Drs Vitovski and Sayers); and Public Health Laboratory, Gwynedd General Hospital, Bangor, Wales (Ms Dunkin and Dr Howard). Dr Howard is currently with the Department of Medical Microbiology and Public Health Laboratory, University Hospital of Wales, Heath Park, Cardiff.
Context Nontypeable Haemophilus influenzae strains
form part of the normal flora of the human upper respiratory tract but are
also implicated in a wide range of diseases. Infections caused by nontypeable H influenzae are major health and socioeconomic burdens.
No single bacterial trait has been associated with disease as opposed to colonization.
Objectives To compare IgA1 protease activity in nontypeable H influenzae strains isolated from patients with symptomatic Haemophilus infection (sputum, cerebrospinal fluid, blood,
or normally sterile tissue) vs strains from throat swabs of asymptomatic carriers
and to compare iga gene carriage and variability
in nontypeable H influenzae strains.
Design and Setting Retrospective study of 63 strains (44 clinical and 19 carriage) collected
between 1991 and 2000 and maintained at the Public Health Laboratory, Gwynedd
General Hospital, Bangor, Wales.
Main Outcome Measures Levels of IgA1 protease activity produced by carriage strains and clinical
isolates from symptomatic patients; the determination of the size and sequence
of a variable region of the iga gene.
Results Bacterial IgA1 protease activity was significantly higher (P<.001) in strains isolated from sputum, blood, cerebrospinal fluid,
or normally sterile tissue of symptomatic individuals (median, 155 mU; interquartile
range [IQR], 80-220 mU; mean, 169 mU; 95% confidence interval [CI], 126-211
mU) than in those isolated from throat swabs of asymptomatic carriers (median,
30 mU; IQR, 15-90 mU; mean, 56 mU; 95% CI, 26-86 mU; assayed on secretory
IgA). The iga gene was detected in 97% of all strains
examined. Variations in the sizes and sequences of part of the iga genes were also apparent. This variable region encodes a polypeptide
linker connecting the protease domain to the β-core autotranslocator,
a porelike structure required for secretion of the protease.
Conclusions These findings reveal the importance of iga
gene variability and expression levels in the establishment of disease phenotype.
They identify nontypeable H influenzae IgA1 protease
as a virulence factor and as a potential target for the development of new
strategies to fight these important pathogens.
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