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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004301naa a2200433 4500
001oai:DiVA.org:umu-99393
003SwePub
008150207s2014 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-993932 URI
0247 a https://doi.org/10.1128/mBio.02038-142 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Greene, Sarah E.4 aut
2451 0a Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli
264 1c 2014
338 a electronic2 rdacarrier
520 a Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the fimS promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the fimS phase off orientation, and this effect was necessary for the majority of ec240's inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the fimS promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic Escherichia coli (UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound. IMPORTANCE CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.
650 7a NATURVETENSKAPx Kemix Organisk kemi0 (SwePub)104052 hsv//swe
650 7a NATURAL SCIENCESx Chemical Sciencesx Organic Chemistry0 (SwePub)104052 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Mikrobiologi inom det medicinska området0 (SwePub)301092 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Microbiology in the medical area0 (SwePub)301092 hsv//eng
7001 a Pinkner, Jerome S.4 aut
7001 a Chorell, Eriku Umeå universitet,Kemiska institutionen4 aut0 (Swepub:umu)erkchl00
7001 a Dodson, Karen W.4 aut
7001 a Shaffer, Carrie L.4 aut
7001 a Conover, Matt S.4 aut
7001 a Livny, Jonathan4 aut
7001 a Hadjifrangiskou, Maria4 aut
7001 a Almqvist, Fredriku Umeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR)4 aut0 (Swepub:umu)fral0001
7001 a Hultgren, Scott J.4 aut
7102 a Umeå universitetb Kemiska institutionen4 org
7730 t mBiog 5:6, s. UNSP e02038-q 5:6<UNSP e02038-x 2161-2129x 2150-7511
8564 u https://doi.org/10.1128/mBio.02038-14y Fulltext
8564 u https://umu.diva-portal.org/smash/get/diva2:788698/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-99393
8564 8u https://doi.org/10.1128/mBio.02038-14

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