scholarly journals Shutting DownShigellaSecretion: Characterizing Small Molecule Type Three Secretion System ATPase Inhibitors

Biochemistry ◽  
2018 ◽  
Vol 57 (50) ◽  
pp. 6906-6916 ◽  
Author(s):  
Heather B. Case ◽  
Dominic S. Mattock ◽  
Nicholas E. Dickenson
Keyword(s):  
Small Molecule ◽  
Secretion System ◽  
Type Three Secretion System ◽  
Atpase Inhibitors ◽  
Type Three Secretion ◽  
Molecule Type

scholarly journals Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Anna B. Sheremet ◽  
Naylia A. Zigangirova ◽  
Egor S. Zayakin ◽  
Sergei I. Luyksaar ◽  
Lydia N. Kapotina ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Secretion System ◽  
Resistant Bacteria ◽  
Lung Pathology ◽  
Antibiotic Resistant ◽  
Molecule Inhibitor ◽  
Type Three Secretion System ◽  
Type Three Secretion

Pseudomonas aeruginosais a cause of high mortality in burn, immunocompromised, and surgery patients. High incidence of antibiotic resistance in this pathogen makes the existent therapy inefficient. Type three secretion system (T3SS) is a leading virulence system ofP. aeruginosathat actively suppresses host resistance and enhances the severity of infection. Innovative therapeutic strategies aiming at inhibition of type three secretion system ofP. aeruginosaare highly attractive, as they may reduce the severity of clinical manifestations and improve antibacterial immune responses. They may also represent an attractive therapy for antibiotic-resistant bacteria. Recently our laboratory developed a new small molecule inhibitor belonging to a class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT), that effectively suppressed T3SS in chlamydia and salmonellain vitroandin vivo.In this study, we evaluate the activity of FT towards antibiotic-resistant clinical isolates ofP. aeruginosaexpressing T3SS effectors ExoU and ExoS in an airway infection model. We found that FT reduced mortality and bacterial loads and decrease lung pathology and systemic inflammation. In addition, we show that FT inhibits the secretion of ExoT and ExoY, reduced bacteria cytotoxicity, and increased bacteria internalizationin vitro. Overall, FT shows a strong potential as an antibacterial therapy of antibiotic-resistantP. aeruginosainfection.

scholarly journals Novel Noncompetitive Type Three Secretion System ATPase Inhibitors Shut Down Shigella Effector Secretion

Biochemistry ◽  
2020 ◽  
Vol 59 (28) ◽  
pp. 2667-2678
Author(s):  
Heather B. Case ◽  
Dominic S. Mattock ◽  
Bill R. Miller ◽  
Nicholas E. Dickenson
Keyword(s):  
Secretion System ◽  
Type Three Secretion System ◽  
Atpase Inhibitors ◽  
Effector Secretion ◽  
Type Three Secretion

An inhibitory mechanism of action of coiled‐coil peptides against type three secretion system from enteropathogenicEscherichia coli

2019 ◽  
Vol 25 (3) ◽  
Author(s):  
Mariano Larzábal ◽  
Hector A. Baldoni ◽  
Fernando D. Suvire ◽  
Lucrecia M. Curto ◽  
Gabriela E. Gomez ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Coiled Coil ◽  
Secretion System ◽  
Inhibitory Mechanism ◽  
Type Three Secretion System ◽  
Type Three Secretion

scholarly journals Plasmid composition in Aeromonas salmonicida subsp. salmonicida 01-B526 unravels unsuspected type three secretion system loss patterns

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine H. Tanaka ◽  
Antony T. Vincent ◽  
Jean-Guillaume Emond-Rheault ◽  
Marcin Adamczuk ◽  
Michel Frenette ◽  
...  
Keyword(s):  
Secretion System ◽  
Aeromonas Salmonicida ◽  
Type Three Secretion System ◽  
Type Three Secretion

scholarly journals Type Three Secretion System-Dependent Microvascular Thrombosis and Ischemic Enteritis in Human Gut Xenografts Infected with Enteropathogenic Escherichia coli

2017 ◽  
Vol 85 (11) ◽  
Author(s):  
Einat Nissim-Eliraz ◽  
Eilam Nir ◽  
Irit Shoval ◽  
Noga Marsiano ◽  
Israel Nissan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Blood Vessels ◽  
Secretion System ◽  
Infection Model ◽  
Apical Surface ◽  
Muscularis Mucosa ◽  
Human Gut ◽  
Type Three Secretion System ◽  
Type Three Secretion ◽  
Ischemic Enteritis

ABSTRACT Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS), causing the hallmark attaching and effacing (AE) lesions and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models. We therefore established an EPEC infection model in human gut xenografts in SCID mice and used it to study the role of T3SS in the pathogenesis of the disease. Following EPEC O127:H6 strain E2348/69 infection, T3SS-dependent AE lesions and pedestals were demonstrated in all infected xenografts. We report here the development of T3SS-dependent intestinal thrombotic microangiopathy (iTMA) and ischemic enteritis in ∼50% of infected human gut xenografts. Using species-specific CD31 immunostaining, we showed that iTMA was limited to the larger human-mouse chimeric blood vessels, which are located between the muscularis mucosa and circular muscular layer of the human gut. These blood vessels were massively invaded by bacteria, which adhered to and formed pedestals on endothelial cells and aggregated with mouse neutrophils in the lumen. We conclude that endothelial infection, iTMA, and ischemic enteritis might be central mechanisms underlying severe EPEC-mediated disease.

Aeromonas salmonicida Ati2 is an effector protein of the type three secretion system

Microbiology ◽  
2013 ◽  
Vol 159 (Pt_9) ◽  
pp. 1937-1945 ◽  
Author(s):  
Stéphanie Dallaire-Dufresne ◽  
Xavier Barbeau ◽  
Darren Sarty ◽  
Katherine H. Tanaka ◽  
Alix M. Denoncourt ◽  
...  
Keyword(s):  
Secretion System ◽  
Aeromonas Salmonicida ◽  
Effector Protein ◽  
Type Three Secretion System ◽  
Type Three Secretion
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