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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, cell surface plasmin activity of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA). Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate; *, p < 0.05; ***, p < 0.001; ns, not significantly different. Plus sign (+) indicates cultures grown in the presence of human plasminogen; minus sign (−), indicates cultures grown in the absence of human plasminogen. B, bacterial survival of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA) following exposure to human neutrophils. Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate. ***, p < 0.001; ns, not significantly different. C, Kaplan-Meier survival curves for nonencapsulated M4 GAS (M4 pDCerm, n = 20; M4 ΔhylA pDCerm, n = 10), encapsulated M4 GAS (M4 pHasABC, n = 20; M4 ΔhylA pHasABC, n = 10).
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Figure 7: A, cell surface plasmin activity of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA). Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate; *, p < 0.05; ***, p < 0.001; ns, not significantly different. Plus sign (+) indicates cultures grown in the presence of human plasminogen; minus sign (−), indicates cultures grown in the absence of human plasminogen. B, bacterial survival of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA) following exposure to human neutrophils. Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate. ***, p < 0.001; ns, not significantly different. C, Kaplan-Meier survival curves for nonencapsulated M4 GAS (M4 pDCerm, n = 20; M4 ΔhylA pDCerm, n = 10), encapsulated M4 GAS (M4 pHasABC, n = 20; M4 ΔhylA pHasABC, n = 10).

Mentions: The accumulation of plasmin activity on the cell surface is correlated with invasive disease propensity, enabling GAS to degrade host tissue barriers and spread systemically from the site of localized infection (5). M4 GAS is frequently associated with severe invasive human infections (33, 63), so we assessed the capacity of M4 GAS to acquire plasmin activity. M4 WT and ΔhylA accumulated significantly less plasmin than WT M1 GAS (Fig. 7A), the serotype most often associated with severe invasive GAS infections (4). Capsule expression in WT M4 and M4 ΔhylA improved plasmin activity (Fig. 7A), and bacterial survival following a 15-min exposure to freshly isolated human neutrophils ex vivo (Fig. 7B). However, capsule expression did not enhance the virulence of WT M4 or M4 ΔhylA in a mouse model of systemic infection (Fig. 7C). The HylA-deficient mutant M4 ΔhylA did not display a significant reduction in virulence compared with M4 WT (Fig. 7C). Together, these data suggest that capsule expression may not provide a survival advantage for M4 GAS.


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, cell surface plasmin activity of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA). Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate; *, p < 0.05; ***, p < 0.001; ns, not significantly different. Plus sign (+) indicates cultures grown in the presence of human plasminogen; minus sign (−), indicates cultures grown in the absence of human plasminogen. B, bacterial survival of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA) following exposure to human neutrophils. Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate. ***, p < 0.001; ns, not significantly different. C, Kaplan-Meier survival curves for nonencapsulated M4 GAS (M4 pDCerm, n = 20; M4 ΔhylA pDCerm, n = 10), encapsulated M4 GAS (M4 pHasABC, n = 20; M4 ΔhylA pHasABC, n = 10).
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Figure 7: A, cell surface plasmin activity of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA). Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate; *, p < 0.05; ***, p < 0.001; ns, not significantly different. Plus sign (+) indicates cultures grown in the presence of human plasminogen; minus sign (−), indicates cultures grown in the absence of human plasminogen. B, bacterial survival of nonencapsulated M4 GAS (WT and ΔhylA), encapsulated M4 GAS (M4 pHasABC and M4 ΔhylA pHasABC), encapsulated WT M1 GAS, and nonencapsulated M1 GAS (M1 ΔhasA) following exposure to human neutrophils. Values denote arithmetic mean ± S.E. Data were pooled and normalized to M1 from 2 independent experiments, each performed in triplicate. ***, p < 0.001; ns, not significantly different. C, Kaplan-Meier survival curves for nonencapsulated M4 GAS (M4 pDCerm, n = 20; M4 ΔhylA pDCerm, n = 10), encapsulated M4 GAS (M4 pHasABC, n = 20; M4 ΔhylA pHasABC, n = 10).
Mentions: The accumulation of plasmin activity on the cell surface is correlated with invasive disease propensity, enabling GAS to degrade host tissue barriers and spread systemically from the site of localized infection (5). M4 GAS is frequently associated with severe invasive human infections (33, 63), so we assessed the capacity of M4 GAS to acquire plasmin activity. M4 WT and ΔhylA accumulated significantly less plasmin than WT M1 GAS (Fig. 7A), the serotype most often associated with severe invasive GAS infections (4). Capsule expression in WT M4 and M4 ΔhylA improved plasmin activity (Fig. 7A), and bacterial survival following a 15-min exposure to freshly isolated human neutrophils ex vivo (Fig. 7B). However, capsule expression did not enhance the virulence of WT M4 or M4 ΔhylA in a mouse model of systemic infection (Fig. 7C). The HylA-deficient mutant M4 ΔhylA did not display a significant reduction in virulence compared with M4 WT (Fig. 7C). Together, these data suggest that capsule expression may not provide a survival advantage for M4 GAS.

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