Repurposing of statins for Buruli Ulcer treatment: antimicrobial activity against Mycobacterium ulcerans
Open accessAbstract
Mycobacterium ulcerans causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not promptly treated, these lesions can lead to severe disfigurement and disability. The standard antibiotic regimen for Buruli Ulcer treatment has been oral rifampicin combined with intramuscular streptomycin administered daily for 8 weeks. However, there has been a recent shift toward replacing streptomycin with oral clarithromycin. Despite the advantages of this antibiotic regimen, it is limited by low compliance, associated side effects, and refractory efficacy for severe ulcerative lesions. Therefore, new drug candidates with a safer pharmacological spectrum and easier mode of administration are needed. Statins are lipid-lowering drugs broadly used for dyslipidemia treatment but have also been reported to have several pleiotropic effects, including antimicrobial activity against fungi, parasites, and bacteria. In the present study, we tested the susceptibility of M. ulcerans to several statins, namely atorvastatin, simvastatin, lovastatin and fluvastatin. Using broth microdilution assays and cultures of M. ulcerans-infected macrophages, we found that atorvastatin, simvastatin and fluvastatin had antimicrobial activity against M. ulcerans. Furthermore, when using the in vitro checkerboard assay, the combinatory additive effect of atorvastatin and fluvastatin with the standard antibiotics used for Buruli Ulcer treatment highlighted the potential of statins as adjuvant drugs. In conclusion, statins hold promise as potential treatment options for Buruli Ulcer. Further studies are necessary to validate their effectiveness and understand the mechanism of action of statins against M. ulcerans.
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Statins exhibit a broad spectrum of biological activities, including antimicrobial, antiparasitic, antibacterial, antiviral, and antifungal potential.
“Moreover, statins exhibit a broad spectrum of biological activities, including antimicrobial, antiparasitic, antibacterial, antiviral, and antifungal potential [110, 111, 112, 113].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [111]
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Cites
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566 · see citing works
Drug repositioning: identifying and developing new uses for existing drugs
Ashburn, T. T., & Thor, K. B. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1468 · Cited by 3,237 · see citing works
PLEIOTROPIC EFFECTS OF STATINS
Liao, J. K., & Laufs, U. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095748 · Cited by 1,994 · see citing works
Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update
Schächter, M. (2004) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2004.00299.x · Cited by 1,216 · see citing works
New insights into the pharmacodynamic and pharmacokinetic properties of statins
Corsini, A., Bellosta, S., Baetta, R., Fumagalli, R., Paoletti, R., & Bernini, F. (1999) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(99)00045-5 · Cited by 796 · see citing works
Essential Role for Cholesterol in Entry of Mycobacteria into Macrophages
Gatfield, J., & Pieters, J. (2000) · Science · doi:10.1126/science.288.5471.1647 · Cited by 615 · see citing works
A historical perspective on the discovery of statins
Endo, A. (2010) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.86.484 · Cited by 550 · see citing works
When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing
Doern, C. D. (2014) · Journal of Clinical Microbiology · doi:10.1128/jcm.01121-14 · Cited by 434 · see citing works
Stinear, T. P., Seemann, T., Pidot, S. J., Frigui, W., Reysset, G., Garnier, T., Meurice, G., Simon, D., Bouchier, C., Ma, L., et al. (2007) · Genome Research · doi:10.1101/gr.5942807 · Cited by 392 · see citing works
The fractional inhibitory concentration (FIC) index as a measure of synergy
Hall, M. J., Middleton, R. F., & Westmacott, D. (1983) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/11.5.427 · Cited by 350 · see citing works
Parihar, S. P., Guler, R., Khutlang, R., Lang, D. M., Hurdayal, R., Mhlanga, M., Suzuki, H., Marais, A. D., & Brombacher, F. (2014) · Journal of Infectious Diseases · doi:10.1093/infdis/jit550 · Cited by 295 · see citing works
VanderVen, B. C., Fahey, R. J., Lee, W., Liu, Y., Abramovitch, R. B., Memmott, C., Crowe, A. M., Eltis, L. D., Perola, E., Deininger, D. D., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004679 · Cited by 264 · see citing works
Hydrophilic or Lipophilic Statins?
Climent, E., Benaiges, D., & Pedro‐Botet, J. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.687585 · Cited by 252 · see citing works
Etuaful, S., Carbonnelle, B., Grosset, J. H. E., Lucas, S. B., Horsfield, C. J., Phillips, R. O., Evans, M. R. W., Ofori‐Adjei, D., Klustse, E., Owusu-Boateng, J., et al. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.8.3182-3186.2005 · Cited by 238 · see citing works
Yam, K. C., D’Angelo, I., Kalscheuer, R., Zhu, H., Wang, J.-X., Snieckus, V. A., Ly, L. H., Converse, P. J., Jacobs, W. R., Strynadka, N. C. J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000344 · Cited by 225 · see citing works
What is a relevant statin concentration in cell experiments claiming pleiotropic effects?
Björkhem‐Bergman, L., Lindh, J. D., & Bergman, P. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2011.03907.x · Cited by 207 · see citing works
Chauty, A., Ardant, M.-F., Adeye, A., Euverte, H., Guédénon, A., Johnson, C. R., Aubry, J., Nuermberger, E. L., & Grosset, J. H. E. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00175-07 · Cited by 205 · see citing works
Nesbitt, N. M., Yang, X., Fontán, P. A., Kolesnikova, I., Smith, I., Sampson, N. S., & Dubnau, E. (2009) · Infection and Immunity · doi:10.1128/iai.00893-09 · Cited by 198 · see citing works
Mycobacterium tuberculosis Is Able To Accumulate and Utilize Cholesterol
Brzostek, A. M., Pawełczyk, J., Rumijowska-Galewicz, A., Dziadek, B. R., & Dziadek, J. (2009) · Journal of Bacteriology · doi:10.1128/jb.00488-09 · Cited by 171 · see citing works
Hypercholesterolemia Impairs Immunity to Tuberculosis
Martens, G. W., Arıkan, M., Lee, J., Ren, F., Vallerskog, T., & Kornfeld, H. (2008) · Infection and Immunity · doi:10.1128/iai.00037-08 · Cited by 150 · see citing works
Is There Potential for Repurposing Statins as Novel Antimicrobials?
Hennessy, E., Adams, C., Reen, F. J., & O’Gara, F. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00192-16 · Cited by 131 · see citing works
Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection
Lovewell, R. R., Sassetti, C. M., & VanderVen, B. C. (2015) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.10.002 · Cited by 125 · see citing works
Simvastatin increases the in vivo activity of the first-line tuberculosis regimen
Skerry, C. M., Pinn, M. L., Bruiners, N., Pine, R. I., Gennaro, M. L., & Karakousis, P. C. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku166 · Cited by 119 · see citing works
3-Ketosteroid 9α-hydroxylase is an essential factor in the pathogenesis ofMycobacterium tuberculosis
Hu, Y., van der Geize, R., Besra, G. S., Gurcha, S. S., Liu, A., Rohde, M., Singh, M., & Coates, A. R. M. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06957.x · Cited by 118 · see citing works
Phillips, R. O., Robert, J., Abass, K. M., Thompson, W. A., Sarfo, F. S., Tuah, W., Sarpong, G. K., Gateau, T., Chauty, A., Omollo, R., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30047-7 · Cited by 114 · see citing works
Statins Increase Rifampin Mycobactericidal Effect
Lobato, L. S., Rosa, P. S., Ferreira, J. D. S., Neumann, A. D. S., da Silva, M. G., do Nascimento, D. C., Soares, C. T., Pedrini, S. C. B., de Oliveira, D. S. L., Monteiro, C. P., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01826-13 · Cited by 110 · see citing works
Cholesterol Metabolism Increases the Metabolic Pool of Propionate in Mycobacterium tuberculosis
Yang, X., Nesbitt, N. M., Dubnau, E., Smith, I., & Sampson, N. S. (2009) · Biochemistry · doi:10.1021/bi9005418 · Cited by 105 · see citing works
Sequence Comparisons Reveal Two Classes of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase
Bochar, D. A., Stauffacher, C. V., & Rodwell, V. W. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1998.2786 · Cited by 99 · see citing works
Montero, M. T., Hernández, O., Suárez, Y., Matilla, J., Ferruelo, A. J., Martı́nez-Botas, J., Gómez-Coronado, D., & Lasunción, M. A. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(00)00417-2 · Cited by 97 · see citing works
A checkerboard method to evaluate interactions between drugs
Martínez-Irujo, J. J., Villahermosa, M. L., Alberdi, E. M., & Santiago, E. (1996) · Biochemical Pharmacology · doi:10.1016/s0006-2952(95)02230-9 · Cited by 90 · see citing works
Adjunctive Host-Directed Therapy With Statins Improves Tuberculosis-Related Outcomes in Mice
Dutta, N. K., Bruiners, N., Zimmerman, M. D., Tan, S., Dartois, V. A., Gennaro, M. L., & Karakousis, P. C. (2019) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz517 · Cited by 90 · see citing works
Evolution of foamy macrophages in the pulmonary granulomas of experimental tuberculosis models
Cáceres, N., Tapia, G., Ojanguren, I., Altare, F., Gil, O., Pinto, S., Vilaplana, C., & Cardona, P.-J. (2008) · Tuberculosis · doi:10.1016/j.tube.2008.11.001 · Cited by 81 · see citing works
Wilding, E. I., Kim, D.-Y., Bryant, A. P., Gwynn, M. N., Lunsford, R. D., McDevitt, D., Myers, J. E., Rosenberg, M. J., Sylvester, D., Stauffacher, C. V., et al. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.18.5147-5152.2000 · Cited by 80 · see citing works
Bischoff, K. M., & Rodwell, V. W. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.1.19-23.1996 · Cited by 75 · see citing works
O'Brien, D. P., Jenkin, G., Buntine, J. A., Steffen, C. M., McDonald, A., Horne, S., Friedman, N. D., Athan, E., Hughes, A. J., Callan, P., et al. (2013) · The Medical Journal of Australia · doi:10.5694/mja13.11331 · Cited by 71 · see citing works
Loike, J. D., Shabtai, D., Neuhut, R., Malitzky, S., lu, E. E. A., Husemann, J., Goldberg, I. J., & Silverstein, S. C. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000143858.15909.29 · Cited by 69 · see citing works
Frimpong, M., Agbavor, B., Duah, M. S., Loglo, A. D., Sarpong, F. N., Boakye-Appiah, J. K., Abass, K. M., Dongyele, M., Amofa, G., Tuah, W., et al. (2019) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007689 · Cited by 65 · see citing works
Mycobacterium Tuberculosis Metabolism and Host Interaction: Mysteries and Paradoxes
Ehrt, S., & Rhee, K. Y. (2012) · Current topics in microbiology and immunology · doi:10.1007/82_2012_299 · Cited by 62 · see citing works
The potent effect of mycolactone on lipid membranes
Nitenberg, M., Bénarouche, A., Maniti, O., Marion, E., Marsollier, L., Géan, J., Dufourc, É. J., Cavalier, J., Canaan, S., & Girard-Egrot, A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006814 · Cited by 42 · see citing works
Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection
Fraga, A. G., Trigo, G., Murthy, R. K., Akhtar, S., Hebbur, M., Pacheco, A. R. F., Dominguez, J., Silva-Gomes, R., Gonçalves, C. M., Oliveira, H., et al. (2019) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0007113 · Cited by 39 · see citing works
Self-citationSoh, A. Z., Chee, C. B.-E., Wang, Y. T., Yuan, J., & Koh, W. (2016) · Journal of Nutrition · doi:10.3945/jn.115.228049 · Cited by 36 · see citing works
Repurposing of Existing Statin Drugs for Treatment of Microbial Infections: How Much Promising?
Rana, R., Sharma, R., & Kumar, A. (2018) · Infectious Disorders - Drug Targets · doi:10.2174/1871526518666180806123230 · Cited by 36 · see citing works
Dual coenzyme specificity of Archaeoglobus fulgidus HMG‐CoA reductase
Kim, D., Stauffacher, C. V., & Rodwell, V. W. (2000) · Protein Science · doi:10.1110/ps.9.6.1226 · Cited by 35 · see citing works
Mycolactone: More than Just a Cytotoxin
Guenin‐Macé, L., Ruf, M., Pluschke, G., & Demangel, C. (2019) · Springer eBooks · doi:10.1007/978-3-030-11114-4_7 · Cited by 35 · see citing works
Pommelet, V., Vincent, Q. B., Ardant, M.-F., Adeye, A., Tanase, A., Tondeur, L., Rega, A., Landier, J., Marion, E., Alcaïs, A., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu584 · Cited by 29 · see citing works
Liao, K., Lin, C., & Lai, S. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00597 · Cited by 25 · see citing works
Sugawara, M., Ishii, N., Nakanaga, K., Suzuki, K., Umebayashi, Y., Makigami, K., & Aihara, M. (2015) · The Journal of Dermatology · doi:10.1111/1346-8138.12851 · Cited by 20 · see citing works
Comparison of Minimum Inhibitory Concentration (MIC) value of statin drugs: A Systematic Review
Gupta, M., & Kumar, A. (2018) · Anti-Infective Agents · doi:10.2174/2211352516666180629124433 · Cited by 20 · see citing works
Metabolomic profiles delineate mycolactone signature in Buruli ulcer disease
Niang, F., Sarfo, F. S., Frimpong, M., Guenin‐Macé, L., Wansbrough-Jones, M. H., Stinear, T. P., Phillips, R. O., & Demangel, C. (2015) · Scientific Reports · doi:10.1038/srep17693 · Cited by 15 · see citing works
Compliance with Antimicrobial Therapy for Buruli Ulcer
Klis, S., Kingma, R. A., Tuah, W., Stienstra, Y., & van der Werf, T. S. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03763-14 · Cited by 13 · see citing works
Owusu, E., Newman, M. J., Kotey, N. K., Akumwena, A., & Bannerman, E. (2016) · International Journal of Microbiology · doi:10.1155/2016/8304524 · Cited by 12 · see citing works
Buruli ulcer: cured by 8 weeks of oral antibiotics?
Johnson, P. D. R. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30478-5 · Cited by 12 · see citing works
Robbe-Saule, M., Foulon, M., Poncin, I., Esnault, L., Varet, H., Legendre, R., Besnard, A., Grzegorzewicz, A. E., Jackson, M., Canaan, S., et al. (2021) · Virulence · doi:10.1080/21505594.2021.1929749 · Cited by 10 · see citing works
Buruli ulcer: a new case definition for Victoria
Betts, J. M., Tay, E. L., Johnson, P. D. R., Lavender, C. J., Gibney, K. B., O'Brien, D. P., Globan, M., Tzimourtas, N., O’Hara, M., & Crouch, S. R. (2020) · Communicable Diseases Intelligence · doi:10.33321/cdi.2020.44.93 · Cited by 9 · see citing works
Meregildo-Rodríguez, E. D., Chunga-Chévez, E. V., Gianmarco, R.-A. L., & Vásquez-Tirado, G. A. (2022) · Infezioni in Medicina · doi:10.53854/liim-3002-4 · Cited by 8 · see citing works
Statins Alter Lipid Bilayer Properties
Sanford, R. L., Alaref, S. J., Koeppe, R. E., & Andersen, O. S. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2012.11.515 · Cited by 6 · see citing works
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- Authors
- Dominguez, J., Mendes, A. I., Pacheco, A. R., Peixoto, M. J., Pedrosa, J., & Fraga, A. G.
- Affiliations
- University of Minho (PT)
- Corresponding author
- Fraga, Alexandra G.
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2023-09-29
- Volume
- 14
- Pages
- 1266261-1266261
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC10570734
- OpenAlex
- W4387213184
- Cited by
- 4
- References
- 56
- Citations by year
- 2025: 2 · 2024: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Indian National Science Academy
- Secretaría de Educación Superior, Ciencia, Tecnología e Innovación
- Fundação para a Ciência e a Tecnologia (01-0145, UIDB/50026/2020, PORTUGAL 2020, NORTE-01-0145-FEDER-085468, UIDP/50026/2020, NORTE2020, NORTE‐01‐0145‐FEDER‐000039, NORTE-01-0145)
- European Regional Development Fund (UIDP/50026/2020, PORTUGAL2020, NORTE-01-0145-FEDER-000039, UIDB/50026/2020, NORTE-2020)
- Topics
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
- Keywords
- Buruli ulcer, Mycobacterium ulcerans, statins, antimicrobial activity, atorvastatin, simvastatin, fluvastatin, lovastatin, drug repurposing, adjuvant therapy, combination therapy, pleiotropy, macrophage infection
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