Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria from Filarial Nematodes in Vivo

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 May 16

PMID 22586066

Citations 37

Authors

Andrea Schiefer

Alexander Schmitz

Till F Schaberle

Sabine Specht

Christine Lammer

Kelly L Johnston

Dmitry G Vassylyev

Gabriele M Konig

Achim Hoerauf

Kenneth Pfarr

Affiliations

Soon will be listed here.

Abstract

Doxycycline and rifampicin deplete essential Wolbachia from filarial nematodes that cause lymphatic filariasis or onchocerciasis, resulting in blocked worm development and death. However, doxycycline is contraindicated for children and pregnant/breastfeeding women, as is rifampicin in the latter group with the additional specter of possible resistance development in Mycobacterium spp. Novel antibiotics with a narrower spectrum would aid in eliminating filarial diseases. Corallococcus coralloides synthesizes corallopyronin A, a noncompetitive inhibitor of RNA polymerase ineffective against Mycobacterium spp. Corallopyronin A depleted Wolbachia from infected insect cells (1.89 Thus the antibiotic is effective against intracellular bacteria despite the many intervening surfaces (blood vessels, pleura, worm cuticle) and membranes (worm cell, vesicle, Wolbachia inner and outer membranes). Corallopyronin A is an antibiotic to develop further for filariasis elimination without concern for cross-resistance development in tuberculosis.

Citing Articles

Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.

Sussmuth R, Sussmuth R, Kulike-Koczula M, Kulike-Koczula M, Gao P, Kosol S Angew Chem Int Ed Engl. 2024; 64(10):e202414325.

PMID: 39611429 PMC: 11878372. DOI: 10.1002/anie.202414325.

The MraY Inhibitor Muraymycin D2 and Its Derivatives Induce Enlarged Cells in Obligate Intracellular and and Break the Persistence Phenotype in .

Lockener I, Behrmann L, Reuter J, Schiefer A, Klockner A, Krannich S Antibiotics (Basel). 2024; 13(5).

PMID: 38786149 PMC: 11117252. DOI: 10.3390/antibiotics13050421.

A laboratory-based predictive pathway for the development of high-level resistance to corallopyronin A, an inhibitor of bacterial RNA polymerase.

Balthazar J, Golparian D, Unemo M, Read T, Grosse M, Stadler M Microbiol Spectr. 2024; 12(6):e0056024.

PMID: 38647280 PMC: 11237373. DOI: 10.1128/spectrum.00560-24.

Combinations of the azaquinazoline anti- agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis.

Hegde S, Marriott A, Pionnier N, Steven A, Bulman C, Gunderson E Front Microbiol. 2024; 15():1346068.

PMID: 38362501 PMC: 10867176. DOI: 10.3389/fmicb.2024.1346068.

Drug Repurposing in the Chemotherapy of Infectious Diseases.

Hamid A, Maser P, Mahmoud A Molecules. 2024; 29(3).

PMID: 38338378 PMC: 10856722. DOI: 10.3390/molecules29030635.

References

Strubing U, Lucius R, Hoerauf A, Pfarr K . Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes. Int J Parasitol. 2010; 40(10):1193-202. DOI: 10.1016/j.ijpara.2010.03.004. View

Supali T, Djuardi Y, Pfarr K, Wibowo H, Taylor M, Hoerauf A . Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment. Clin Infect Dis. 2008; 46(9):1385-93. DOI: 10.1086/586753. View

Pfarr K, Hoerauf A . Antibiotics which target the Wolbachia endosymbionts of filarial parasites: a new strategy for control of filariasis and amelioration of pathology. Mini Rev Med Chem. 2006; 6(2):203-10. DOI: 10.2174/138955706775475984. View

Mand S, Pfarr K, Sahoo P, Satapathy A, Specht S, Klarmann U . Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine. Am J Trop Med Hyg. 2009; 81(4):702-11. DOI: 10.4269/ajtmh.2009.09-0155. View

Makepeace B, Rodgers L, Trees A . Rate of elimination of Wolbachia pipientis by doxycycline in vitro increases following drug withdrawal. Antimicrob Agents Chemother. 2006; 50(3):922-7. PMC: 1426454. DOI: 10.1128/AAC.50.3.922-927.2006. View

Mukhopadhyay J, Das K, Ismail S, Koppstein D, Jang M, Hudson B . The RNA polymerase "switch region" is a target for inhibitors. Cell. 2008; 135(2):295-307. PMC: 2580802. DOI: 10.1016/j.cell.2008.09.033. View

Clardy J, Fischbach M, Walsh C . New antibiotics from bacterial natural products. Nat Biotechnol. 2006; 24(12):1541-50. DOI: 10.1038/nbt1266. View

Hoerauf A . Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis. Curr Opin Infect Dis. 2008; 21(6):673-81. DOI: 10.1097/QCO.0b013e328315cde7. View

Irschik H, Gerth K, Hofle G, Kohl W, Reichenbach H . The myxopyronins, new inhibitors of bacterial RNA synthesis from Myxococcus fulvus (Myxobacterales). J Antibiot (Tokyo). 1983; 36(12):1651-8. DOI: 10.7164/antibiotics.36.1651. View

10.

Bandi C, McCall J, Genchi C, Corona S, Venco L, Sacchi L . Effects of tetracycline on the filarial worms Brugia pahangi and Dirofilaria immitis and their bacterial endosymbionts Wolbachia. Int J Parasitol. 1999; 29(2):357-64. DOI: 10.1016/s0020-7519(98)00200-8. View

11.

Debrah A, Mand S, Marfo-Debrekyei Y, Batsa L, Pfarr K, Lawson B . Reduction in levels of plasma vascular endothelial growth factor-A and improvement in hydrocele patients by targeting endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline. Am J Trop Med Hyg. 2009; 80(6):956-63. View

12.

ONeill A, Oliva B, Storey C, Hoyle A, Fishwick C, Chopra I . RNA polymerase inhibitors with activity against rifampin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother. 2000; 44(11):3163-6. PMC: 101622. DOI: 10.1128/AAC.44.11.3163-3166.2000. View

13.

Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner D . Depletion of wolbachia endobacteria in Onchocerca volvulus by doxycycline and microfilaridermia after ivermectin treatment. Lancet. 2001; 357(9266):1415-6. DOI: 10.1016/S0140-6736(00)04581-5. View

14.

Hoerauf A, Schmetz C, Blaxter M, Buttner D, Gallin M, Al-Qaoud K . Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility. J Clin Invest. 1999; 103(1):11-8. PMC: 407866. DOI: 10.1172/JCI4768. View

15.

Hoerauf A, Pfarr K, Mand S, Debrah A, Specht S . Filariasis in Africa--treatment challenges and prospects. Clin Microbiol Infect. 2011; 17(7):977-85. DOI: 10.1111/j.1469-0691.2011.03586.x. View

16.

Esterre P, Plichart C, Sechan Y, Nguyen N . The impact of 34 years of massive DEC chemotherapy on Wuchereria bancrofti infection and transmission: the Maupiti cohort. Trop Med Int Health. 2001; 6(3):190-5. DOI: 10.1046/j.1365-3156.2001.00682.x. View

17.

Kozek W . Transovarially-transmitted intracellular microorganisms in adult and larval stages of Brugia malayi. J Parasitol. 1977; 63(6):992-1000. View

18.

LARKIN M, Blackshields G, Brown N, Chenna R, McGettigan P, McWilliam H . Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21):2947-8. DOI: 10.1093/bioinformatics/btm404. View

19.

Debrah A, Mand S, Specht S, Marfo-Debrekyei Y, Batsa L, Pfarr K . Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis. PLoS Pathog. 2006; 2(9):e92. PMC: 1564427. DOI: 10.1371/journal.ppat.0020092. View

20.

Osei-Atweneboana M, Awadzi K, Attah S, Boakye D, Gyapong J, Prichard R . Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus. PLoS Negl Trop Dis. 2011; 5(3):e998. PMC: 3066159. DOI: 10.1371/journal.pntd.0000998. View