title: A type III secretion system inhibitor targets YopD while revealing differential regulation of secretion in calcium-blind mutants of Yersinia pestis.
abstract: 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 Pseudomonas aeruginosa. YopD, a protein involved in the formation of the translocon and regulatory processes of the type III secretion system, appears to play a role in the inhibition of secretion by compound D. The use of compound D in T3S regulatory mutants demonstrated a difference in secretion inhibition in the presence and absence of calcium. Interestingly, compound D was effective only under conditions without calcium, indicating that a secretion-active needle structure may be necessary for compound D to inhibit secretion.
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Jessen
authors.forename: David S
authors.initials: DS
authors.lastname: Bradley
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Nilles
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000187:drug effects* / Q000235:genetics; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003408:Cresols / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015010:Yersinia pestis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; D003408:Cresols; C078910:YopD protein, Yersinia; D002118:Calcium