title: Inhibitors of macrophage infectivity potentiator-like PPIases affect neisserial and chlamydial pathogenicity.
abstract: The pathogenic bacteria Chlamydia trachomatis, Neisseria gonorrhoeae and Neisseria meningitidis express the surface-exposed macrophage infectivity potentiator (MIP)-like protein, which plays a role in their pathogenicity. MIP exhibits a peptidyl-prolyl isomerase (PPIase) activity that is inhibited by rapamycin and FK506. In this study, pipecolic acid derivatives were tested for their activity against the chlamydial and neisserial MIP. Two MIP inhibitors were identified, PipN3 and PipN4, that affected the developmental cycle of C. trachomatis in HeLa cells. Furthermore, we could show that deletion of neisserial MIP or addition of the two MIP inhibitors affected the survival of N. gonorrhoeae in the presence of neutrophils. Furthermore, both compounds inhibited the adherence, invasion and/or survival of N. meningitidis in epithelial cells. These results confirm the importance of MIP-like proteins in infection and indicate the relevance of pipecolic acid derivatives as antimicrobials against C. trachomatis, N. gonorrhoeae and N. meningitidis.
authors: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors: Anastasija
authors: A
authors: Reimer
authors: Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors: Florian
authors: F
authors: Seufert
authors: Department of Enzymology, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors: Matthias
authors: M
authors: Weiwad
authors: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors: Jutta
authors: J
authors: Ebert
authors: Marshall Center for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
authors: Nicole M
authors: NM
authors: Bzdyl
authors: Marshall Center for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
authors: Charlene M
authors: CM
authors: Kahler
authors: Marshall Center for Infectious Disease Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia; Defence Science and Technology Laboratory, Biomedical Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors: Mitali
authors: M
authors: Sarkar-Tyson
authors: Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors: Ulrike
authors: U
authors: Holzgrabe
authors: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors: Thomas
authors: T
authors: Rudel
authors: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, 97074 Würzburg, Germany. Electronic address: Vera.Kozjak@uni-wuerzburg.de.
authors: Vera
authors: V
authors: Kozjak-Pavlovic
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D055786:Gene Knockout Techniques; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D009344:Neisseria gonorrhoeae / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C077482:Mip-like protein, Chlamydia trachomatis
keywords: Chlamydia trachomatis; Macrophage infectivity potentiator; Neisseria gonorrhoeae; Neisseria meningitidis; Pipecolic acid derivatives