group A streptococcus
Research Article | Host-Microbe BiologyIntracellular Group A Streptococcus Induces Golgi Fragmentation To Impair Host Defenses through Streptolysin O and NAD-GlycohydrolaseTwo prominent virulence factors of group A Streptococcus (GAS), streptolysin O (SLO) and NAD-glycohydrolase (Nga), are linked to enhanced pathogenicity of the prevalent GAS strains. Recent advances show that SLO and Nga are important for intracellular survival of GAS in epithelial cells and macrophages.
Research Article | Molecular Biology and PhysiologyRole of Glutathione in Buffering Excess Intracellular Copper in Streptococcus pyogenesThe control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it has been established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity....
Research Article | Host-Microbe BiologyExPortal and the LiaFSR Regulatory System Coordinate the Response to Cell Membrane Stress in Streptococcus pyogenesBacterial two-component systems sense and induce transcriptional changes in response to environmental stressors, including antimicrobials and human antimicrobial peptides. Since the stresses imposed by the host’s defensive responses may act as markers of specific temporal stages of disease progression or host compartments, pathogens often coordinately regulate stress response programs with virulence factor expression. The mechanism by...
Research Article | Host-Microbe BiologyT4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 Streptococcus pyogenesGroup A Streptococcus (GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that...
Research Article | Molecular Biology and PhysiologyThe Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated Streptococcus pyogenes InfectionsBiofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and...
Research Article | Host-Microbe BiologyIntegrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during InfectionAutophagy is generally considered a strategy used by the innate immune system to eliminate invasive pathogens through capturing and transferring them to lysosomes. Currently, researchers pay more attention to how virulence factors secreted by GAS regulate the autophagic process. Here, we provide the first evidence that the structural protein FbaA of M1 GAS strain SF370 is a potent inducer of autophagy in epithelial cells. Furthermore,...
Research Article | Therapeutics and PreventionVaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing AntibodiesAvailability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by...
Research Article | Ecological and Evolutionary ScienceThe Emergence of Successful Streptococcus pyogenes Lineages through Convergent Pathways of Capsule Loss and Recombination Directing High Toxin ExpressionStreptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for the majority of human infection in high-income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that...
Research Article | Therapeutics and PreventionA Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across SerotypesGAS is among the most common human pathogens and causes a wide variety of diseases, likely more than any other microorganism. The diverse clinical manifestations of GAS may be attributable to its large repertoire of virulence factors that are selectively and synergistically involved in streptococcal pathogenesis. To date, GAS vaccines have not been successful due to multiple serotypes and postinfection sequelae associated with...
Research Article | Host-Microbe BiologyA Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like ProteinsM proteins are surface-anchored virulence factors in group A streptococci, human pathogens. Here, we identified an M-like protein, SzM, and its positive regulator, SezV, in Streptococcus equi subspecies zooepidemicus (SEZ), an important group of pathogens for domesticated animals, including horses and pigs. SzM and SezV homologues were found in the genomes of...