Yersinia pestis type III secretion system-dependent inhibition of human polymorphonuclear leukocyte function.

Polymorphonuclear Leukocyte Function System-Dependent Inhibition of Human Type III Secretion Yersinia pestis

A type III secretion system inhibitor targets YopD while revealing differential regulation of secretion in calcium-blind mutants of Yersinia pestis.

Numerous Gram-negative pathogens rely upon type III secretion (T3S) systems to cause disease. Several small-molecule inhibitors of the type III secretion systems have been identified; however, few targets of these inhibitors have been elucidated. Here we report that 2,2'-thiobis-(4-methylphenol) (compound D), inhibits type III secretion in Yersinia pestis, Yersinia pseudotuberculosis, and Pseud...

Targeting type III secretion in Yersinia pestis.

Yersinia pestis, the causative agent of plague, utilizes a plasmid-encoded type III secretion system (T3SS) to aid it with its resistance to host defenses. This system injects a set of effector proteins known as Yops (Yersinia outer proteins) into the cytosol of host cells that come into contact with the bacteria. T3SS is absolutely required for the virulence of Y. pestis, making it a potential...

Neutrophils Are Resistant to Yersinia YopJ/P-Induced Apoptosis and Are Protected from ROS-Mediated Cell Death by the Type III Secretion System

BACKGROUND The human innate immune system relies on the coordinated activity of macrophages and polymorphonuclear leukocytes (neutrophils or PMNs) for defense against bacterial pathogens. Yersinia spp. subvert the innate immune response to cause disease in humans. In particular, the Yersinia outer protein YopJ (Y. pestis and Y. pseudotuberculosis) and YopP (Y. enterocolitica) rapidly induce apo...

Identification of Small-Molecule Inhibitors of Yersinia pestis Type III Secretion System YscN ATPase

Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain...