Mutual Exclusivity of Hyaluronan and Hyaluronidase in Invasive Group A Streptococcus

Henningham, Anna; Yamaguchi, M.; Aziz, Ramy K.; Kuipers, Kirsten; Buffalo, Cosmo Z.; Dahesh, Samira; Choudhury, Biswa; Vleet, Jeremy Van; Yamaguchi, Yuka; Seymour, Lisa M.; Zakour, Nouri L. Ben; He, Lingjun; Smith, Helen; Grimwood, Keith; Beatson, Scott A.; Ghosh, Partho; Walker, Mark J.; Nizet, Victor; Cole, Jason N.

doi:10.1074/jbc.m114.602847

Cited by 30 publications

(36 citation statements)

References 70 publications

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“…Although this seems unexpected, it is not unusual for enzyme levels to impact S. aureus biofilm development, as other extracellular matrix-degrading enzymes must be repressed or surface proteins and extracellular DNA (eDNA) will be destroyed (42,43). Additionally, such a dichotomy is not unusual among bacterial pathogens, as Streptococcus pyogenes secretes a hyaluronidase while simultaneously producing a HA capsule, resulting in a biological state that appears mutually exclusive (44).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

et al. 2016

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Staphylococcus aureus is a leading cause of chronic biofilm infections. Hyaluronic acid (HA) is a large glycosaminoglycan abundant in mammalian tissues that has been shown to enhance biofilm formation in multiple Gram-positive pathogens. We observed that HA accumulated in an S. aureus biofilm infection using a murine implant-associated infection model and that HA levels increased in a mutant strain lacking hyaluronidase (HysA). S. aureus secretes HysA in order to cleave HA during infection. Through in vitro biofilm studies with HA, the hysA mutant was found to accumulate increased biofilm biomass compared to the wild type, and confocal microscopy showed that HA is incorporated into the biofilm matrix. Exogenous addition of purified HysA enzyme dispersed HA-containing biofilms, while catalytically inactive enzyme had no impact. Additionally, induction of hysA expression prevented biofilm formation and also dispersed an established biofilm in the presence of HA. These observations were corroborated in the implant model, where there was decreased dissemination from an hysA mutant biofilm infection compared to the S. aureus wild type. Histopathology demonstrated that infection with an hysA mutant caused significantly reduced distribution of tissue inflammation compared to wild-type infection. To extend these studies, the impact of HA and S. aureus HysA on biofilm-like aggregates found in joint infections was examined. We found that HA contributes to the formation of synovial fluid aggregates, and HysA can disrupt aggregate formation. Taken together, these studies demonstrate that HA is a relevant component of the S. aureus biofilm matrix and HysA is important for dissemination from a biofilm infection.

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Section: Discussionmentioning

confidence: 99%

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

et al. 2016

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“…Thus, M4 isolates may possess unknown antiphagocytic factor(s) enhancing adhesion and invasion. 81 )…”

Section: Virulence Factors That May Contribute To the Pathogenesis Ofmentioning

confidence: 99%

Molecular and genomic characterization of pathogenic traits of group A <i>Streptococcus pyogenes</i>

Hamada

Kawabata

Nakagawa

2015

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85–1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these.

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“…12,13 In many cases, high-level amplification or homozygous deletion may be necessary to activate an oncogene or to inactivate a tumor suppressor gene. 14 Positively associated amplifications (co-occurrence) indicate the relevant genes may function in synergy to promote oncogenesis, 15,16 whereas anticorrelated (mutual exclusive) CNAs often represent functional redundancies in similar pathways. Therefore, the relationships between CNAs events may help to identify oncogenic network modules.…”

Section: Introductionmentioning

confidence: 98%

Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers

et al. 2015

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Colorectal cancer (CRC) results from the accumulation of genetic alterations, and somatic copy number alterations (CNAs) are crucial for the development of CRC. Genome-wide survey of CNAs provides opportunities for identifying cancer driver genes in an unbiased manner. The detection of aberrant CNAs may provide novel markers for the early diagnosis and personalized treatment of CRC. A major challenge in array-based profiling of CNAs is to distinguish the alterations that play causative roles from the random alterations that accumulate during colorectal carcinogenesis. In this view, we systematically discuss the frequent CNAs in CRC, focusing on functional genes that have potential diagnostic, prognostic and therapeutic significance.

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Mutual Exclusivity of Hyaluronan and Hyaluronidase in Invasive Group A Streptococcus

Cited by 30 publications

References 70 publications

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

Hyaluronan Modulation Impacts Staphylococcus aureus Biofilm Infection

Molecular and genomic characterization of pathogenic traits of group A <i>Streptococcus pyogenes</i>

Somatic gene copy number alterations in colorectal cancer: new quest for cancer drivers and biomarkers

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