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Antimicrobial agents and chemotherapy2012; 56(4); 1749-1755; doi: 10.1128/AAC.05797-11

In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment.

Abstract: Rhodococcus equi, the causal agent of rhodococcosis, is a severe pathogen of foals but also of immunodeficient humans, causing bronchopneumonia. The pathogen is often found together with Klebsiella pneumoniae or Streptococcus zooepidemicus in foals. Of great concern is the fact that some R. equi strains are already resistant to commonly used antibiotics. In the present study, we evaluated the in vitro potential of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, as new drugs against R. equi and its associated pathogens. The peptides led to growth inhibition and death of R. equi and S. zooepidemicus at low micromolar concentrations. Moreover, eCATH1 was able to inhibit growth of K. pneumoniae. Both peptides caused rapid disruption of the R. equi membrane, leading to cell lysis. Interestingly, eCATH1 had a synergic effect together with rifampin. Furthermore, eCATH1 was not cytotoxic against mammalian cells at bacteriolytic concentrations and maintained its high killing activity even at physiological salt concentrations. Our data suggest that equine AMPs, especially eCATH1, may be promising candidates for alternative drugs to control R. equi in mono- and coinfections.
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Publication Date: 2012-01-09 PubMed ID: 22232283PubMed Central: PMC3318344DOI: 10.1128/AAC.05797-11Google Scholar: Lookup
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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.

The research paper evaluates the in vitro effectiveness of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, in treating rhodococcosis, a severe disease in foals and immunodeficient humans. The study found that these peptides can inhibit growth and cause death of Rhodococcus equi and other pathogens, presenting a potential alternative to conventional antibiotics that these pathogens are becoming resistant to.

Antimicrobial Peptides as Potential Therapeutics

  • The study focused on the testing of two equine AMPs (antimicrobial peptides), eCATH1 and DEFA1, in vitro. These AMPs were chosen for their potential as new drugs that could successfully combat the bacteria R. equi and other associated pathogens that often cause rhodococcosis.
  • Inhibiting and causing the death of R. equi and S. zooepidemicus, another pathogen commonly found in foals, were achieved by the peptides at low micromolar concentrations, indicating their effectiveness.

Inhibition of Pathogens

  • Even more promising was the finding that eCATH1 was able to stop the growth of the bacterium K. pneumoniae. This shows the broad-spectrum potential of eCATH1 as an antimicrobial agent.
  • The two AMPs also caused rapid disruption of the R. equi membrane, leading to cell lysis, or the breakdown of the pathogen’s cell.

Synergistic Effect and Cytotoxicity

  • The study also found a synergistic effect between eCATH1 and rifampin, meaning that the two drugs worked more efficiently in combination than each would on its own. This suggests the potential for combination therapies in treating R. equi infections.
  • Importantly, eCATH1 was found not to be cytotoxic against mammalian cells at bacteriolytic concentrations, which means it could potentially be used safely as a treatment.
  • Under physiological salt concentrations, eCATH1 maintained its high killing activity. This indicates robust performance under conditions that would be faced during actual clinical use.

Potential for Alternative Drug Development

  • The research suggests that equine AMPs, and eCATH1 in particular, can be promising candidates for the development of new drugs aimed at controlling R. equi, whether alone or co-infected with other pathogens.
  • This potential is particularly important considering the alarming fact that some R. equi strains have developed resistance to commonly used antibiotics currently on the market.

Cite This Article

APA
Schlusselhuber M, Jung S, Bruhn O, Goux D, Leippe M, Leclercq R, Laugier C, Grötzinger J, Cauchard J. (2012). In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment. Antimicrob Agents Chemother, 56(4), 1749-1755. https://doi.org/10.1128/AAC.05797-11

Publication

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
NlmUniqueID: 0315061
Country: United States
Language: English
Volume: 56
Issue: 4
Pages: 1749-1755

Researcher Affiliations

Schlusselhuber, Margot
  • Bacteriology and Parasitology Unit, Dozulé Laboratory for Equine Diseases, ANSES, Goustranville, Dozulé, France. margot.schlusselhuber@anses.fr
Jung, Sascha
    Bruhn, Oliver
      Goux, Didier
        Leippe, Matthias
          Leclercq, Roland
            Laugier, Claire
              Grötzinger, Joachim
                Cauchard, Julien

                  MeSH Terms

                  • Actinomycetales Infections / drug therapy
                  • Actinomycetales Infections / microbiology
                  • Actinomycetales Infections / veterinary
                  • Animals
                  • Anti-Bacterial Agents / chemistry
                  • Anti-Bacterial Agents / pharmacology
                  • Cell Survival / drug effects
                  • Chlorocebus aethiops
                  • Circular Dichroism
                  • Drug Resistance, Bacterial
                  • Drug Synergism
                  • Female
                  • Hemolysis
                  • Horse Diseases / drug therapy
                  • Horse Diseases / microbiology
                  • Horses
                  • Liposomes / chemistry
                  • Microbial Sensitivity Tests
                  • Microscopy, Electron, Scanning
                  • Phospholipids / chemistry
                  • Rhodococcus equi / drug effects
                  • Rhodococcus equi / ultrastructure
                  • Salt Tolerance
                  • Sheep
                  • Vero Cells
                  • alpha-Defensins / chemistry
                  • alpha-Defensins / pharmacology

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