RRC ID 63735
Author Nozawa T, Iibushi J, Toh H, Minowa-Nozawa A, Murase K, Aikawa C, Nakagawa I.
Title Intracellular Group A Streptococcus Induces Golgi Fragmentation To Impair Host Defenses through Streptolysin O and NAD-Glycohydrolase.
Journal mBio
Abstract Group A Streptococcus (GAS; Streptococcus pyogenes) is a major human pathogen that causes streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as streptococcal toxic-shock syndrome. During infection, GAS not only invades diverse host cells but also injects effector proteins such as NAD-glycohydrolase (Nga) into the host cells through a streptolysin O (SLO)-dependent mechanism without invading the cells; Nga and SLO are two major virulence factors that are associated with increased bacterial virulence. Here, we have shown that the invading GAS induces fragmentation of the Golgi complex and inhibits anterograde transport in the infected host cells through the secreted toxins SLO and Nga. GAS infection-induced Golgi fragmentation required both bacterial invasion and SLO-mediated Nga translocation into the host cytosol. The cellular Golgi network is critical for the sorting of surface molecules and is thus essential for the integrity of the epithelial barrier and for the immune response of macrophages to pathogens. In epithelial cells, inhibition of anterograde trafficking by invading GAS and Nga resulted in the redistribution of E-cadherin to the cytosol and an increase in bacterial translocation across the epithelial barrier. Moreover, in macrophages, interleukin-8 secretion in response to GAS infection was found to be suppressed by intracellular GAS and Nga. Our findings reveal a previously undescribed bacterial invasion-dependent function of Nga as well as a previously unrecognized GAS-host interaction that is associated with GAS pathogenesis.IMPORTANCE Two 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. Here, we found that invading GAS disrupts the Golgi complex in host cells through SLO and Nga. We show that GAS-induced Golgi fragmentation requires bacterial invasion into host cells, SLO pore formation activity, and Nga NADase activity. GAS-induced Golgi fragmentation results in the impairment of the epithelial barrier and chemokine secretion in macrophages. This immune inhibition property of SLO and Nga by intracellular GAS indicates that the invasion of GAS is associated with virulence exerted by SLO and Nga.
Volume 12(1)
Published 2021-2-9
DOI 10.1128/mBio.01974-20
PII mBio.01974-20
PMID 33563838
PMC PMC7885101
MeSH A549 Cells Bacterial Proteins / genetics Bacterial Proteins / metabolism Cytoplasm / microbiology Epithelial Cells / microbiology* Golgi Apparatus / genetics Golgi Apparatus / microbiology Golgi Apparatus / pathology* HeLa Cells Host-Pathogen Interactions / genetics* Host-Pathogen Interactions / immunology Humans Interleukin-8 / immunology NAD+ Nucleosidase / genetics* NAD+ Nucleosidase / metabolism Streptococcal Infections / microbiology Streptococcus pyogenes / immunology Streptococcus pyogenes / pathogenicity* Streptolysins / genetics* Streptolysins / metabolism THP-1 Cells Virulence Factors
IF 6.784
Human and Animal Cells CACO-2(RCB0988)