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

Henningham A, Yamaguchi M, Aziz RK, Kuipers K, Buffalo CZ, Dahesh S, Choudhury B, Van Vleet J, Yamaguchi Y, Seymour LM, Ben Zakour NL, He L, Smith HV, Grimwood K, Beatson SA, Ghosh P, Walker MJ, Nizet V, Cole JN - J. Biol. Chem. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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A, PFGE typing of 17 clinical M4 GAS isolates associated with invasive disease. Data are representative of 2 independent experiments. B, mid-log phase capsule expression levels for M4 strains SP435–SP451 and M1 strain 5448. Values denote arithmetic mean ± S.E. Data were pooled and normalized to 5448 from 2 independent experiments, each performed in triplicate. C, monosaccharide composition analysis of hydrolyzed glycosaminoglycan (GAG)-enriched fractions from WT M4 GAS, encapsulated WT M1 GAS control strain 5448AP (22), and 1 nmol standards. Abbreviations used are: Fuc, fucose; GalNH2, galactosamine; GlcNH2, glucosamine; Gal, galactose; Glc, glucose; Man, mannose; GalA, galacturonic acid; GlcA, glucuronic acid.
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Figure 1: A, PFGE typing of 17 clinical M4 GAS isolates associated with invasive disease. Data are representative of 2 independent experiments. B, mid-log phase capsule expression levels for M4 strains SP435–SP451 and M1 strain 5448. Values denote arithmetic mean ± S.E. Data were pooled and normalized to 5448 from 2 independent experiments, each performed in triplicate. C, monosaccharide composition analysis of hydrolyzed glycosaminoglycan (GAG)-enriched fractions from WT M4 GAS, encapsulated WT M1 GAS control strain 5448AP (22), and 1 nmol standards. Abbreviations used are: Fuc, fucose; GalNH2, galactosamine; GlcNH2, glucosamine; Gal, galactose; Glc, glucose; Man, mannose; GalA, galacturonic acid; GlcA, glucuronic acid.

Mentions: Over the past few decades, M1 GAS has been the most frequently isolated serotype from human infections worldwide (4) and the leading cause of life-threatening invasive syndromes (5). However, serotype M4 was the principal serotype associated with a recent report of severe invasive infections in Queensland, Australia, accounting for 16% of isolates compared with 8% for M1 (34). 17 such M4 isolates from this region, designated SP435–SP451, were obtained from children aged 1 to 14 years with invasive GAS infections between 2001 and 2009 (Table 1). SP435 and SP436 were highly virulent strains isolated from brothers hospitalized for 2–3 weeks (supplemental Table S1). The worldwide resurgence of severe invasive GAS infections over the past three decades has been attributed to the emergence of a single globally disseminated serotype M1T1 GAS clone (20). To determine whether the M4 isolates were clonal in origin, genomic DNA extracts were analyzed by PFGE. Three distinct PFGE patterns were identified, with the majority (65%) of M4 isolates sharing the same pattern (Fig. 1A). MLST classified the strains into 2 groups, with 15 of 17 (88%) identified as ST 39 (Table 1). SP449 and SP451 share a unique and hitherto unidentified mutS allele (supplemental Table S2), and have yet to be assigned a ST by the S. pyogenes MLST database.


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

Henningham A, Yamaguchi M, Aziz RK, Kuipers K, Buffalo CZ, Dahesh S, Choudhury B, Van Vleet J, Yamaguchi Y, Seymour LM, Ben Zakour NL, He L, Smith HV, Grimwood K, Beatson SA, Ghosh P, Walker MJ, Nizet V, Cole JN - J. Biol. Chem. (2014)

A, PFGE typing of 17 clinical M4 GAS isolates associated with invasive disease. Data are representative of 2 independent experiments. B, mid-log phase capsule expression levels for M4 strains SP435–SP451 and M1 strain 5448. Values denote arithmetic mean ± S.E. Data were pooled and normalized to 5448 from 2 independent experiments, each performed in triplicate. C, monosaccharide composition analysis of hydrolyzed glycosaminoglycan (GAG)-enriched fractions from WT M4 GAS, encapsulated WT M1 GAS control strain 5448AP (22), and 1 nmol standards. Abbreviations used are: Fuc, fucose; GalNH2, galactosamine; GlcNH2, glucosamine; Gal, galactose; Glc, glucose; Man, mannose; GalA, galacturonic acid; GlcA, glucuronic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231703&req=5

Figure 1: A, PFGE typing of 17 clinical M4 GAS isolates associated with invasive disease. Data are representative of 2 independent experiments. B, mid-log phase capsule expression levels for M4 strains SP435–SP451 and M1 strain 5448. Values denote arithmetic mean ± S.E. Data were pooled and normalized to 5448 from 2 independent experiments, each performed in triplicate. C, monosaccharide composition analysis of hydrolyzed glycosaminoglycan (GAG)-enriched fractions from WT M4 GAS, encapsulated WT M1 GAS control strain 5448AP (22), and 1 nmol standards. Abbreviations used are: Fuc, fucose; GalNH2, galactosamine; GlcNH2, glucosamine; Gal, galactose; Glc, glucose; Man, mannose; GalA, galacturonic acid; GlcA, glucuronic acid.
Mentions: Over the past few decades, M1 GAS has been the most frequently isolated serotype from human infections worldwide (4) and the leading cause of life-threatening invasive syndromes (5). However, serotype M4 was the principal serotype associated with a recent report of severe invasive infections in Queensland, Australia, accounting for 16% of isolates compared with 8% for M1 (34). 17 such M4 isolates from this region, designated SP435–SP451, were obtained from children aged 1 to 14 years with invasive GAS infections between 2001 and 2009 (Table 1). SP435 and SP436 were highly virulent strains isolated from brothers hospitalized for 2–3 weeks (supplemental Table S1). The worldwide resurgence of severe invasive GAS infections over the past three decades has been attributed to the emergence of a single globally disseminated serotype M1T1 GAS clone (20). To determine whether the M4 isolates were clonal in origin, genomic DNA extracts were analyzed by PFGE. Three distinct PFGE patterns were identified, with the majority (65%) of M4 isolates sharing the same pattern (Fig. 1A). MLST classified the strains into 2 groups, with 15 of 17 (88%) identified as ST 39 (Table 1). SP449 and SP451 share a unique and hitherto unidentified mutS allele (supplemental Table S2), and have yet to be assigned a ST by the S. pyogenes MLST database.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus