Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus

Henningham, Anna and Yamaguchi, Masaya and Aziz, Ramy K. and Kuipers, Kirsten and Buffalo, Cosmo Z. and Dahesh, Samira and Choudhury, Biswa and Van Vleet, Jeremy and Yamaguchi, Yuka and Seymour, Lisa M. and Ben Zakour, Nouri L. and He, Lingjun and Smith, Helen V. and Grimwood, Keith and Beatson, Scott A. and Ghosh, Partho and Walker, Mark J. and Nizet, Victor and Cole, Jason N. (2014) Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus. Journal of Biological Chemistry, 289 (46). pp. 32303-32315. ISSN 0021-9258

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Abstract

A recent analysis of group A Streptococcus (GAS) invasive infections in Australia has shown a predominance of M4 GAS, a serotype recently reported to lack the antiphagocytic hyaluronic acid (HA) capsule. Here, we use molecular genetics and bioinformatics techniques to characterize 17 clinical M4 isolates associated with invasive disease in children during this recent epidemiology. All M4 isolates lacked HA capsule, and whole genome sequence analysis of two isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Conversely, M4 isolates possess a functional HA-degrading hyaluronate lyase (HylA) enzyme that is rendered nonfunctional in other GAS through a point mutation. Transformation with a plasmid expressing hasABC restored partial encapsulation in wild-type (WT) M4 GAS, and full encapsulation in an isogenic M4 mutant lacking HylA. However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection. Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition. These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2014 by The American Society for Biochemistry and Molecular Biology. Open access article - Creative Commons
Faculty / Department / School: Current - Faculty of Health, Engineering and Sciences - No Department
Date Deposited: 08 Apr 2015 06:32
Last Modified: 10 Apr 2015 03:59
Uncontrolled Keywords: bacterial pathogenesis; group A Streptococcus; hyaluronan; hyaluronate; hyaluronate lyase; hyaluronic acid capsule; infectious disease; invasive disease; nonencapsulated; Streptococcus Pyogenes (S. Pyogenes)
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110302 Clinical Chemistry (diagnostics)
11 Medical and Health Sciences > 1108 Medical Microbiology > 110802 Medical Infection Agents (incl. Prions)
06 Biological Sciences > 0605 Microbiology > 060502 Infectious Agents
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases
Identification Number or DOI: 10.1074/jbc.M114.602847
URI: http://eprints.usq.edu.au/id/eprint/26908

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