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J Biol Chem. 2014 Nov 14;289(46):32303-15. doi: 10.1074/jbc.M114.602847. Epub 2014 Sep 29.

Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus.

Author information

1
From the Department of Pediatrics, the School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, Queensland 4072, Australia.
2
From the Department of Pediatrics, the Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.
3
Systems Biology Research Group, the Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
4
From the Department of Pediatrics, the Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, 6500 HC Nijmegen, The Netherlands.
5
Department of Chemistry and Biochemistry.
6
From the Department of Pediatrics.
7
Glycobiology Research and Training Center, University of California San Diego, La Jolla, California 92093.
8
the School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, Queensland 4072, Australia.
9
the Department of Mathematics and Statistics, San Diego State University, San Diego, California 92182.
10
the Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland 4108, Australia.
11
the Queensland Children's Medical Research Institute, Herston, Queensland 4029, Australia, and.
12
From the Department of Pediatrics, Skaggs School of Pharmacy and Pharmaceutical Sciences, and the Rady Children's Hospital, San Diego, California 92123.
13
From the Department of Pediatrics, the School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, Queensland 4072, Australia, jncole@ucsd.edu.

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.

KEYWORDS:

Bacterial Pathogenesis; Group A Streptococcus; Hyaluronan; Hyaluronate; Hyaluronate Lyase; Hyaluronic acid Capsule; Infectious Disease; Invasive Disease; Nonencapsulated; Streptococcus Pyogenes (S. Pyogenes)

PMID:
25266727
PMCID:
PMC4231703
DOI:
10.1074/jbc.M114.602847
[Indexed for MEDLINE]
Free PMC Article

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