scholarly journals An Experimental Pipeline for Initial Characterization of Bacterial Type III Secretion System Inhibitor Mode of Action Using Enteropathogenic Yersinia

2018 ◽  
Vol 8 ◽  
Author(s):  
Jessica M. Morgan ◽  
Hanh N. Lam ◽  
Jocelyn Delgado ◽  
Justin Luu ◽  
Sina Mohammadi ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Mode Of Action ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Initial Characterization ◽  
Enteropathogenic Yersinia ◽  
Bacterial Type

scholarly journals Evidence for alternative quaternary structure in a bacterial Type III secretion system chaperone

2010 ◽  
Vol 10 (1) ◽  
pp. 21 ◽  
Author(s):  
Michael L Barta ◽  
Lingling Zhang ◽  
Wendy L Picking ◽  
Brian V Geisbrecht
Keyword(s):  
Type Iii Secretion ◽  
Quaternary Structure ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Bacterial Type

scholarly journals Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system

2009 ◽  
Vol 19 (5) ◽  
pp. 1340-1343 ◽  
Author(s):  
Toni Kline ◽  
Kathleen C. Barry ◽  
Stona R. Jackson ◽  
Heather B. Felise ◽  
Hai V. Nguyen ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Bacterial Type

scholarly journals Developing Cyclic Peptomers as Broad-Spectrum Gram negative Bacterial Type III Secretion System Inhibitors

2020 ◽  
Author(s):  
Hanh N. Lam ◽  
Tannia Lau ◽  
Adam Lentz ◽  
Jessica Sherry ◽  
Alejandro Cabrera-Cortez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chlamydia Trachomatis ◽  
Broad Spectrum ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Type Iii ◽  
Bacterial Type

ABSTRACTAntibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS basal bodies detected on the surface of Y. enterocolitica, as visualized using a fluorescent derivative of YscD, an inner membrane ring with low homology to flagellar protein FliG. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly.IMPORTANCETraditional antibiotics target both pathogenic and commensal bacteria, resulting in a disruption of the microbiota, which in turn is tied to a number of acute and chronic diseases. The bacterial type III secretion system (T3SS) is an appendage used by many bacterial pathogens to establish infection, but is largely absent from commensal members of the microbiota. In this study, we identify a new derivative of the cyclic peptomer class of T3SS inhibitors. These compounds inhibit the T3SS of the nosocomial ESKAPE pathogen Pseudomonas aeruginosa and enteropathogenic Yersinia and Salmonella. The impact of cyclic peptomers is specific to the T3SS, as other bacterial secretory systems are unaffected. Importantly, cyclic peptomers completely block replication of Chlamydia trachomatis, the causative agent of genital, eye, and lung infections, in human cells, a process that requires the T3SS. Therefore, cyclic peptomers represent promising virulence blockers that can specifically disarm a broad spectrum of Gram-negative pathogens.

scholarly journals A colorimetric assay for studying effector secretion through the bacterial type III secretion system

2008 ◽  
Vol 278 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Masami Miyake ◽  
Sadatsugu Sakane ◽  
Chiho Kobayashi ◽  
Miyuki Hanajima-Ozawa ◽  
Aya Fukui ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Colorimetric Assay ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Effector Secretion ◽  
Bacterial Type

scholarly journals Structure of a bacterial type III secretion system in contact with a host membrane in situ

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea Nans ◽  
Mikhail Kudryashev ◽  
Helen R. Saibil ◽  
Richard D. Hayward
Keyword(s):  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Iii ◽  
Host Membrane ◽  
Bacterial Type
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