Analyze Diet
Antimicrobial agents and chemotherapy2013; 57(10); 4615-4621; doi: 10.1128/AAC.02044-12

The equine antimicrobial peptide eCATH1 is effective against the facultative intracellular pathogen Rhodococcus equi in mice.

Abstract: Rhodococcus equi, the causal agent of rhodococcosis, is a major pathogen of foals and is also responsible for severe infections in immunocompromised humans. Of great concern, strains resistant to currently used antibiotics have emerged. As the number of drugs that are efficient in vivo is limited because of the intracellular localization of the bacterium inside macrophages, new active but cell-permeant drugs will be needed in the near future. In the present study, we evaluated, by in vitro and ex vivo experiments, the ability of the alpha-helical equine antimicrobial peptide eCATH1 to kill intracellular bacterial cells. Moreover, the therapeutic potential of the peptide was assessed in experimental rhodococcosis induced in mice, while the in vivo toxicity was evaluated by behavioral and histopathological analysis. The study revealed that eCATH1 significantly reduced the number of bacteria inside macrophages. Furthermore, the bactericidal potential of the peptide was maintained in vivo at doses that appeared to have no visible deleterious effects for the mice even after 7 days of treatment. Indeed, daily subcutaneous injections of 1 mg/kg body weight of eCATH1 led to a significant reduction of the bacterial load in organs comparable to that obtained after treatment with 10 mg/kg body weight of rifampin. Interestingly, the combination of the peptide with rifampin showed a synergistic interaction in both ex vivo and in vivo experiments. These results emphasize the therapeutic potential that eCATH1 represents in the treatment of rhodococcosis.
Publication Date: 2013-07-01 PubMed ID: 23817377PubMed Central: PMC3811442DOI: 10.1128/AAC.02044-12Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored the effectiveness of the antimicrobial peptide eCATH1, derived from horses, in combating the intracellular bacterium Rhodococcus equi in mice. Its findings show that eCATH1 significantly reduces the number of bacteria in cells and its potential in treating rhodococcosis without harmful effects to the mice.

Introduction

  • The research revolves around Rhodococcus equi, a pathogen that primarily affects foals but also cause severe infections in humans with compromised immune systems.
  • There are concerns about the emergence of antibiotic-resistant strains, and due to the bacterium’s intracellular localization inside macrophages, the number of drugs that can effectively treat this in vivo is limited.
  • Therefore, the researchers aim to explore and create new active drugs that can permeate cells and combat the pathogen more effectively.
  • In this study, the researchers focus on eCATH1, an alpha-helical equine antimicrobial peptide, and evaluate its effectiveness against intracellular bacterial cells.

Methodology

  • The impact of eCATH1 peptide was evaluated through in vitro and ex vivo experiments. The peptide’s therapeutic potential was also assessed through rhodococcosis induced in mice.
  • The researchers also evaluated the in vivo toxicity of the peptide using behavioral and histopathological analysis.

Results

  • The findings demonstrated that eCATH1 significantly reduced the number of bacteria inside macrophages, demonstrating a strong bactericidal potential.
  • The study also showed that the bactericidal potential of the peptide was maintained in vivo, with no visible deleterious effects on the mice even after 7 days of treatment.
  • Daily subcutaneous injections of 1 mg/kg body weight of eCATH1 led to a significant reduction of the bacterial load in organs, a result comparable to treatment with 10 mg/kg body weight of rifampin, a well-known antibiotic.
  • The combination of the peptide with rifampin showed a synergistic interaction in both ex vivo and in vivo experiments.

Conclusion

  • The research results underscore the therapeutic potential of eCATH1 in the treatment of rhodococcosis by showing its ability to penetrate cells and effectively reduce the bacterial load without causing apparent harm to the host.

Cite This Article

APA
Schlusselhuber M, Torelli R, Martini C, Leippe M, Cattoir V, Leclercq R, Laugier C, Grötzinger J, Sanguinetti M, Cauchard J. (2013). The equine antimicrobial peptide eCATH1 is effective against the facultative intracellular pathogen Rhodococcus equi in mice. Antimicrob Agents Chemother, 57(10), 4615-4621. https://doi.org/10.1128/AAC.02044-12

Publication

ISSN: 1098-6596
NlmUniqueID: 0315061
Country: United States
Language: English
Volume: 57
Issue: 10
Pages: 4615-4621

Researcher Affiliations

Schlusselhuber, Margot
  • Anses, Dozulé Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, Dozulé, France.
Torelli, Riccardo
    Martini, Cecilia
      Leippe, Matthias
        Cattoir, Vincent
          Leclercq, Roland
            Laugier, Claire
              Grötzinger, Joachim
                Sanguinetti, Maurizio
                  Cauchard, Julien

                    MeSH Terms

                    • Actinomycetales Infections / drug therapy
                    • Animals
                    • Anti-Infective Agents / therapeutic use
                    • Cell Line
                    • Macrophages, Peritoneal / microbiology
                    • Mice
                    • Mice, Inbred BALB C
                    • Microscopy, Fluorescence
                    • Rhodococcus equi / drug effects
                    • Rhodococcus equi / pathogenicity
                    • Rifampin / therapeutic use

                    References

                    This article includes 36 references
                    1. Magnusson H. Spezifische infektiose pneumonie biem fohlen. Ein neurer eiterreger biem pferd.. Arch. Wiss. Prakt. Tierheilk. 50:22–38.
                    2. Mauger C. Retrospective study of equine rhodococcosis observed at autopsy on 1617 foals at the “LERPE” (AFSSA, Dozulé) from 1986 to 2006. D.V.M. thesis. Université Paul-Sabatier de Toulouse, Toulouse, France: (In French.).
                    3. Laugier C. Rhodococcose: bilan partiel des cas enregistrés à l'autopsie en 2004 (du 1er janvier au 26 août). Bull. Réseau Epidémiosurveill. Pathol. Equine 13:3.
                    4. Takai S, Sasaki Y, Tsubaki S. Rhodococcus equi infection in foals: current concepts and implication for future research. J. Equine Sci. 6:105–119.
                    5. Yager JA. The pathogenesis of Rhodococcus equi pneumonia in foals.. Vet Microbiol 1987 Aug;14(3):225-32.
                      pubmed: 3314108doi: 10.1016/0378-1135(87)90109-xgoogle scholar: lookup
                    6. Weinstock DM, Brown AE. Rhodococcus equi: an emerging pathogen.. Clin Infect Dis 2002 May 15;34(10):1379-85.
                      pubmed: 11981734doi: 10.1086/340259google scholar: lookup
                    7. Golub B, Falk G, Spink WW. Lung abscess due to Corynebacterium equi. Report of first human infection.. Ann Intern Med 1967 Jun;66(6):1174-7.
                      pubmed: 6067513doi: 10.7326/0003-4819-66-6-1174google scholar: lookup
                    8. Topino S, Galati V, Grilli E, Petrosillo N. Rhodococcus equi infection in HIV-infected individuals: case reports and review of the literature.. AIDS Patient Care STDS 2010 Apr;24(4):211-22.
                      pubmed: 20377432doi: 10.1089/apc.2009.0248google scholar: lookup
                    9. Yamshchikov AV, Schuetz A, Lyon GM. Rhodococcus equi infection.. Lancet Infect Dis 2010 May;10(5):350-9.
                      pubmed: 20417417doi: 10.1016/s1473-3099(10)70068-2google scholar: lookup
                    10. Heidmann P, Madigan JE, watson JL. Rhodococcus equi pneumonia: clinical findings, diagnosis, treatment and prevention. Clin. Tech. Equine Pract. 5:203–2010.
                    11. Asoh N, Watanabe H, Fines-Guyon M, Watanabe K, Oishi K, Kositsakulchai W, Sanchai T, Kunsuikmengrai K, Kahintapong S, Khantawa B, Tharavichitkul P, Sirisanthana T, Nagatake T. Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand.. J Clin Microbiol 2003 Jun;41(6):2337-40.
                    12. Boyen F, Pasmans F, Haesebrouck F. Acquired antimicrobial resistance in equine Rhodococcus equi isolates.. Vet Rec 2011 Jan 29;168(4):101a.
                      pubmed: 21257598doi: 10.1136/vr.c5289google scholar: lookup
                    13. Buckley T, McManamon E, Stanbridge S. Resistance studies of erythromycin and rifampin for Rhodococcus equi over a 10-year period.. Ir Vet J 2007 Dec 1;60(12):728-31.
                      pmc: PMC3113830pubmed: 21851690doi: 10.1186/2046-0481-60-12-728google scholar: lookup
                    14. Kenney DG, Robbins SC, Prescott JF, Kaushik A, Baird JD. Development of reactive arthritis and resistance to erythromycin and rifampin in a foal during treatment for Rhodococcus equi pneumonia.. Equine Vet J 1994 May;26(3):246-8.
                    15. Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.. Nat Biotechnol 2006 Dec;24(12):1551-7.
                      pubmed: 17160061doi: 10.1038/nbt1267google scholar: lookup
                    16. Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses.. Nat Med 2004 Dec;10(12 Suppl):S122-9.
                      pubmed: 15577930doi: 10.1038/nm1145google scholar: lookup
                    17. Zucca M, Savoia D. The post-antibiotic era: promising developments in the therapy of infectious diseases.. Int J Biomed Sci 2010 Jun;6(2):77-86.
                      pmc: PMC3614743pubmed: 23675180
                    18. Steinstraesser L, Kraneburg UM, Hirsch T, Kesting M, Steinau HU, Jacobsen F, Al-Benna S. Host defense peptides as effector molecules of the innate immune response: a sledgehammer for drug resistance?. Int J Mol Sci 2009 Sep 9;10(9):3951-3970.
                      pmc: PMC2769137pubmed: 19865528doi: 10.3390/ijms10093951google scholar: lookup
                    19. Schlusselhuber M, Jung S, Bruhn O, Goux D, Leippe M, Leclercq R, Laugier C, Grötzinger J, Cauchard J. In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment.. Antimicrob Agents Chemother 2012 Apr;56(4):1749-55.
                      pmc: PMC3318344pubmed: 22232283doi: 10.1128/aac.05797-11google scholar: lookup
                    20. Thulin P, Johansson L, Low DE, Gan BS, Kotb M, McGeer A, Norrby-Teglund A. Viable group A streptococci in macrophages during acute soft tissue infection.. PLoS Med 2006 Mar;3(3):e53.
                    21. Verneuil N, Sanguinetti M, Le Breton Y, Posteraro B, Fadda G, Auffray Y, Hartke A, Giard JC. Effects of the Enterococcus faecalis hypR gene encoding a new transcriptional regulator on oxidative stress response and intracellular survival within macrophages.. Infect Immun 2004 Aug;72(8):4424-31.
                    22. Gentry-Weeks CR, Karkhoff-Schweizer R, Pikis A, Estay M, Keith JM. Survival of Enterococcus faecalis in mouse peritoneal macrophages.. Infect Immun 1999 May;67(5):2160-5.
                    23. Takai S, Sasaki Y, Tsubaki S. Influence of inoculation route on virulence of Rhodococcus equi in mice.. Microbiol Immunol 1992;36(8):895-8.
                    24. Nordmann P, Kerestedjian JJ, Ronco E. Therapy of Rhodococcus equi disseminated infections in nude mice.. Antimicrob Agents Chemother 1992 Jun;36(6):1244-8.
                      pmc: PMC190326pubmed: 1416823doi: 10.1128/aac.36.6.1244google scholar: lookup
                    25. Cirioni O, Silvestri C, Ghiselli R, Orlando F, Riva A, Mocchegiani F, Chiodi L, Castelletti S, Gabrielli E, Saba V, Scalise G, Giacometti A. Protective effects of the combination of alpha-helical antimicrobial peptides and rifampicin in three rat models of Pseudomonas aeruginosa infection.. J Antimicrob Chemother 2008 Dec;62(6):1332-8.
                      pubmed: 18799470doi: 10.1093/jac/dkn393google scholar: lookup
                    26. Sharma S, Verma I, Khuller GK. Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis.. Antimicrob Agents Chemother 2001 Feb;45(2):639-40.
                      pmc: PMC90345pubmed: 11158773doi: 10.1128/aac.45.2.639-640.2001google scholar: lookup
                    27. Sharma S, Verma I, Khuller GK. Antibacterial activity of human neutrophil peptide-1 against Mycobacterium tuberculosis H37Rv: in vitro and ex vivo study.. Eur Respir J 2000 Jul;16(1):112-7.
                    28. Jena P, Mishra B, Leippe M, Hasilik A, Griffiths G, Sonawane A. Membrane-active antimicrobial peptides and human placental lysosomal extracts are highly active against mycobacteria.. Peptides 2011 May;32(5):881-7.
                    29. De Yang, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells.. J Exp Med 2000 Oct 2;192(7):1069-74.
                      pmc: PMC2193321pubmed: 11015447doi: 10.1084/jem.192.7.1069google scholar: lookup
                    30. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis.. Immunology 2002 May;106(1):20-6.
                    31. Bowdish DM, Davidson DJ, Speert DP, Hancock RE. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes.. J Immunol 2004 Mar 15;172(6):3758-65.
                      pubmed: 15004180doi: 10.4049/jimmunol.172.6.3758google scholar: lookup
                    32. Bowdish DM, Davidson DJ, Lau YE, Lee K, Scott MG, Hancock RE. Impact of LL-37 on anti-infective immunity.. J Leukoc Biol 2005 Apr;77(4):451-9.
                      pubmed: 15569695doi: 10.1189/jlb.0704380google scholar: lookup
                    33. Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, Roche FM, Mu R, Doho GH, Pistolic J, Powers JP, Bryan J, Brinkman FS, Hancock RE. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37.. J Immunol 2006 Feb 15;176(4):2455-64.
                      pubmed: 16456005doi: 10.4049/jimmunol.176.4.2455google scholar: lookup
                    34. Tan BH, Meinken C, Bastian M, Bruns H, Legaspi A, Ochoa MT, Krutzik SR, Bloom BR, Ganz T, Modlin RL, Stenger S. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens.. J Immunol 2006 Aug 1;177(3):1864-71.
                      pubmed: 16849498doi: 10.4049/jimmunol.177.3.1864google scholar: lookup
                    35. Martens RJ, Cohen ND, Jones SL, Moore TA, Edwards JF. Protective role of neutrophils in mice experimentally infected with Rhodococcus equi.. Infect Immun 2005 Oct;73(10):7040-2.
                    36. Cassone M, Otvos L Jr. Synergy among antibacterial peptides and between peptides and small-molecule antibiotics.. Expert Rev Anti Infect Ther 2010 Jun;8(6):703-16.
                      pubmed: 20521897doi: 10.1586/eri.10.38google scholar: lookup

                    Citations

                    This article has been cited 6 times.
                    1. Wang L, Zhao X, Xia X, Zhu C, Qin W, Xu Y, Hang B, Sun Y, Chen S, Zhang H, Jiang J, Hu J, Fotina H, Zhang G. Antimicrobial Peptide JH-3 Effectively Kills Salmonella enterica Serovar Typhimurium Strain CVCC541 and Reduces Its Pathogenicity in Mice. Probiotics Antimicrob Proteins 2019 Dec;11(4):1379-1390.
                      doi: 10.1007/s12602-019-09533-wpubmed: 31001786google scholar: lookup
                    2. Kamaruzzaman NF, Kendall S, Good L. Targeting the hard to reach: challenges and novel strategies in the treatment of intracellular bacterial infections. Br J Pharmacol 2017 Jul;174(14):2225-2236.
                      doi: 10.1111/bph.13664pubmed: 27925153google scholar: lookup
                    3. Zhao R, Liu Y, Wang H, Yang J, Niu W, Fan S, Xiong W, Ma J, Li X, Phillips JB, Tan M, Qiu Y, Li G, Zhou M. BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway. Cell Mol Immunol 2017 Oct;14(10):830-841.
                      doi: 10.1038/cmi.2016.31pubmed: 27374794google scholar: lookup
                    4. Cauchard S, Van Reet N, Büscher P, Goux D, Grötzinger J, Leippe M, Cattoir V, Laugier C, Cauchard J. Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1. Antimicrob Agents Chemother 2016 May;60(5):2610-9.
                      doi: 10.1128/AAC.01127-15pubmed: 26824936google scholar: lookup
                    5. Bhattacharjya S, Zhang Z, Ramamoorthy A. LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules 2024 Mar 8;14(3).
                      doi: 10.3390/biom14030320pubmed: 38540740google scholar: lookup
                    6. Polinário G, Primo LMDG, Rosa MABC, Dett FHM, Barbugli PA, Roque-Borda CA, Pavan FR. Antimicrobial peptides as drugs with double response against Mycobacterium tuberculosis coinfections in lung cancer. Front Microbiol 2023;14:1183247.
                      doi: 10.3389/fmicb.2023.1183247pubmed: 37342560google scholar: lookup