scholarly journals Gene fitness landscape of group A streptococcus during necrotizing myositis

2019 ◽  
Vol 129 (2) ◽  
pp. 887-901 ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
Matthew Ojeda Saavedra ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Group A Streptococcus ◽  
Necrotizing Myositis ◽  
Group A

scholarly journals Gene fitness landscape of group A streptococcus during necrotizing myositis

2018 ◽  
Author(s):  
Luchang Zhu ◽  
Randall J. Olsen ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
Matthew Ojeda Saavedra ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Group A Streptococcus ◽  
Insertion Site ◽  
Pcr Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Necrotizing Myositis ◽  
Genes Encoding ◽  
Isogenic Mutant Strain ◽  
Group A

ABSTRACTNecrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified novel GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon directed insertion-site sequencing (TraDIS) we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins, and exporters for toxins, quorum sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding five transporters confirmed that each isogenic mutant strain was significantly impaired in causing necrotizing myositis in NHPs. qRT-PCR analysis showed that these five genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface-exposed, suggesting that our findings have translational research implications.

scholarly journals RocA Has Serotype-Specific Gene Regulatory and Pathogenesis Activities in Serotype M28 Group A Streptococcus

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Paul E. Bernard ◽  
Priyanka Kachroo ◽  
Luchang Zhu ◽  
Stephen B. Beres ◽  
Jesus M. Eraso ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Group A Streptococcus ◽  
Specific Gene ◽  
Necrotizing Myositis ◽  
Invasive Infections ◽  
Group A ◽  
Transcription Regulators

ABSTRACTSerotype M28 group A streptococcus (GAS) is a common cause of infections such as pharyngitis (“strep throat”) and necrotizing fasciitis (“flesh-eating” disease). Relatively little is known about the molecular mechanisms underpinning M28 GAS pathogenesis. Whole-genome sequencing studies of M28 GAS strains recovered from patients with invasive infections found an unexpectedly high number of missense (amino acid-changing) and nonsense (protein-truncating) polymorphisms inrocA(regulatorofCov), leading us to hypothesize that altered RocA activity contributes to M28 GAS molecular pathogenesis. To test this hypothesis, an isogenicrocAdeletion mutant strain was created. Transcriptome sequencing (RNA-seq) analysis revealed that RocA inactivation significantly alters the level of transcripts for 427 and 323 genes at mid-exponential and early stationary growth phases, respectively, including genes for 41 transcription regulators and 21 virulence factors. In contrast, RocA transcriptomes from other GAS M protein serotypes are much smaller and include fewer transcription regulators. TherocAmutant strain had significantly increased secreted activity of multiple virulence factors and grew to significantly higher colony counts under acid stressin vitro. RocA inactivation also significantly increased GAS virulence in a mouse model of necrotizing myositis. Our results demonstrate that RocA is an important regulator of transcription regulators and virulence factors in M28 GAS and raise the possibility that naturally occurring polymorphisms inrocAin some fashion contribute to human invasive infections caused by M28 GAS strains.

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

Bilateral periorbital necrotising fasciitis associated with invasive group: a Streptococcus infection

2020 ◽  
Vol 13 (12) ◽  
pp. e236800
Author(s):  
Grace Anne McCabe ◽  
Thomas Hardy ◽  
Thomas Gordon Campbell
Keyword(s):  
Group A Streptococcus ◽  
Early Recognition ◽  
Skin Grafting ◽  
Final Diagnosis ◽  
Necrotising Fasciitis ◽  
Invasive Group ◽  
Group A ◽  
Tissue Microscopy ◽  
Periorbital Swelling ◽  
Multidisciplinary Teamwork

A previously independent 56-year-old immunocompetent woman presented with septic shock in the setting of periorbital swelling and diffuse infiltrates on chest imaging. Blood cultures were positive for growth of group A Streptococcus (GAS). Broad spectrum antimicrobials were initiated with the inclusion of the antitoxin agent clindamycin. Necrosis of periorbital tissue was noted and surgical consultation was obtained. Débridement of both eyelids with skin grafting was performed. GAS was isolated from wound cultures and also observed on periorbital tissue microscopy. The final diagnosis was bilateral periorbital necrotising fasciitis (PONF) associated with invasive GAS infection. The patient had a prolonged intensive care unit course with input from multiple specialist teams. This case demonstrates the importance of early recognition and treatment of PONF, the profound systemic morbidity caused by these infections, and illustrates successful multidisciplinary teamwork.

scholarly journals Genome‐wide analysis of in vivo CcpA binding with and without its key co‐factor HPr in the major human pathogen group A Streptococcus

2020 ◽  
Author(s):  
Sruti DebRoy ◽  
Victor Aliaga‐Tobar ◽  
Gabriel Galvez ◽  
Srishtee Arora ◽  
Xiaowen Liang ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Human Pathogen ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Group A
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