scholarly journals AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus

2021 ◽  
Vol 22 (21) ◽  
pp. 11617
Author(s):  
Nina Tsao ◽  
Ya-Chu Chang ◽  
Sung-Yuan Hsieh ◽  
Tang-Chi Li ◽  
Ching-Chen Chiu ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Group A Streptococcus ◽  
Streptococcal Toxic Shock Syndrome ◽  
Invasive Infection ◽  
Toxic Shock ◽  
Spherical Structures ◽  
Group A ◽  
Bacteria And Fungi

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.

Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010 to 2012

2014 ◽  
Vol 143 (4) ◽  
pp. 864-872 ◽  
Author(s):  
T. IKEBE ◽  
K. TOMINAGA ◽  
T. SHIMA ◽  
R. OKUNO ◽  
H. KUBOTA ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Susceptibility Testing ◽  
Group A Streptococcus ◽  
Sudden Onset ◽  
Control Law ◽  
Streptococcal Toxic Shock Syndrome ◽  
Invasive Infection ◽  
Toxic Shock ◽  
Predominant Genotype ◽  
Group A

SUMMARYStreptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multi-organ failure, and high mortality. In Japan, appropriate notification measures based on the Infectious Disease Control law are mandatory for cases of STSS caused byβ-haemolytic streptococcus. STSS is mainly caused by group A streptococcus (GAS). Although an average of 60–70 cases of GAS-induced STSS are reported annually, 143 cases were recorded in 2011. To determine the reason behind this marked increase, we characterized theemmgenotype of 249 GAS isolates from STSS patients in Japan from 2010 to 2012 and performed antimicrobial susceptibility testing. The predominant genotype was found to beemm1, followed byemm89,emm12,emm28,emm3, andemm90. These six genotypes constituted more than 90% of the STSS isolates. The number ofemm1,emm89,emm12, andemm28isolates increased concomitantly with the increase in the total number of STSS cases. In particular, the number ofmefA-positiveemm1isolates has escalated since 2011. Thus, the increase in the incidence of STSS can be attributed to an increase in the number of cases associated with specific genotypes.

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis

2015 ◽  
Vol 21 (12) ◽  
pp. 873-876 ◽  
Author(s):  
Mayu Hikone ◽  
Ken-ichiro Kobayashi ◽  
Takuya Washino ◽  
Masayuki Ota ◽  
Naoya Sakamoto ◽  
...  
Keyword(s):  
Toxic Shock Syndrome ◽  
Group A Streptococcus ◽  
Streptococcal Toxic Shock Syndrome ◽  
Toxic Shock ◽  
Group A

Group A Streptococcus and hepatitis – streptococcal toxic shock syndrome

2015 ◽  
Vol 04 (03) ◽  
pp. 295-299
Author(s):  
Sanjeev Gupta ◽  
Jarrod Brumby ◽  
Joanna Burton ◽  
Susan Moloney ◽  
Benjamin Kenny
Keyword(s):  
Toxic Shock Syndrome ◽  
Group A Streptococcus ◽  
Streptococcal Toxic Shock Syndrome ◽  
Toxic Shock ◽  
Group A

scholarly journals Clinical Manifestations and Bacterial Genomic Analysis of Group A Streptococcus Strains That Cause Pediatric Toxic Shock Syndrome

2018 ◽  
Vol 8 (3) ◽  
pp. 265-268
Author(s):  
Roman Deniskin ◽  
Brittany Shah ◽  
Flor M Muñoz ◽  
Anthony R Flores
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Toxic Shock Syndrome ◽  
Group A Streptococcus ◽  
Clinical Manifestations ◽  
Streptococcal Toxic Shock Syndrome ◽  
Whole Genome ◽  
Toxic Shock ◽  
Genetic Characteristics ◽  
Group A

Abstract We report here 18 cases of pediatric group A streptococcal toxic shock syndrome, associated clinical findings, and bacterial molecular genetic characteristics discovered through whole-genome sequencing. This comparative whole-genome sequencing revealed unique gene content (speK) and polymorphisms (dpiB) in emm87 group A Streptococcus, the relative contributions of which, in combination with the host response, in the development of streptococcal toxic shock syndrome remain to be elucidated.

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