Targeting the replication initiator of the second Vibrio chromosome: towards generation of vibrionaceae-specific antimicrobial agents.

PLoS Pathogens
Yoshiharu YamaichiMatthew K Waldor

Abstract

The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resi...Continue Reading

References

Apr 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·P J YoungmanR Losick
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Feb 24, 2001·Nature·N T PernaF R Blattner
Jun 5, 2002·Lancet·Tadashi BabaKeiichi Hiramatsu
Aug 28, 2003·Cell·Elizabeth S Egan, Matthew K Waldor
Sep 9, 2004·Microbiology and Molecular Biology Reviews : MMBR·Fabiano L ThompsonJean Swings
Dec 4, 2004·Nature Medicine·Stuart B Levy, Bonnie Marshall
Jan 5, 2005·Journal of Bacteriology·Kazuhisa OkadaTakeshi Honda
Feb 1, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·George H TalbotUNKNOWN Antimicrobial Availability Task Force of the Infectious Diseases Society of America
Jul 28, 2006·Letters in Applied Microbiology·B Austin, X-H Zhang
Jul 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Tatiana Venkova-CanovaDhruba K Chattoraj
Aug 23, 2006·Journal of Bacteriology·Stéphane DuigouMatthew K Waldor
Jan 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yoshiharu YamaichiMatthew K Waldor
Apr 17, 2007·Nature Reviews. Microbiology·Melissa L Mott, James M Berger
Apr 27, 2007·FEMS Microbiology Reviews·Jolanta Zakrzewska-CzerwińskaWalter Messer
Nov 6, 2007·International Journal of Systematic and Evolutionary Microbiology·Cristiane C ThompsonJean Swings
Mar 4, 2008·FEMS Microbiology Letters·Solveig FossumKirsten Skarstad
Jul 22, 2008·Microbial Ecology·Craig Baker-AustinRamunas Stepanauskas
Jul 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Stéphane DuigouMatthew K Waldor
Aug 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Roxana E GeorgescuMike O'Donnell
Oct 31, 2008·ANZ Journal of Surgery·Yi-Chun SuI-Chuan Chen
Jun 23, 2009·Journal of Bacteriology·Leyla Slamti, Matthew K Waldor
Jan 25, 2014·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Erik H KlontzKarl C Klontz

❮ Previous
Next ❯

Citations

Oct 19, 2011·Future Microbiology·Mobashar Hussain Urf Turabe Fazil, Durg V Singh
Aug 4, 2011·PLoS Genetics·Yoshiharu YamaichiMatthew K Waldor
Feb 7, 2012·Biochimica Et Biophysica Acta·Jyoti K JhaDhruba K Chattoraj
Apr 15, 2011·Current Opinion in Microbiology·Tom DefoirdtPeter Bossier
Apr 2, 2014·Antimicrobial Agents and Chemotherapy·Ekaterina GavrishMichael D LaFleur
Apr 24, 2018·Current Drug Discovery Technologies·Rasmus N Klitgaard, Anders Lobner-Olesen
Jan 12, 2017·The Journal of Antimicrobial Chemotherapy·Erika van EijkWiep Klaas Smits
Nov 7, 2019·Bioinformatics and Biology Insights·Harriet U UgbokoJesupemi M Enibukun
Jun 25, 2015·Microbiology Spectrum·Digby F WarnerValerie Mizrahi

❮ Previous
Next ❯

Methods Mentioned

BETA
dynamic light scattering
PCR

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Tatiana Venkova-CanovaDhruba K Chattoraj
Proceedings of the National Academy of Sciences of the United States of America
Stephane DuigouMatthew K Waldor
© 2022 Meta ULC. All rights reserved