In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment.
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.
Bacteriology and Parasitology Unit, Dozulé Laboratory for Equine Diseases, ANSES, Goustranville, Dozulé, France. margot.schlusselhuber@anses.fr
Margot
M
Schlusselhuber
Sascha
S
Jung
Oliver
O
Bruhn
Didier
D
Goux
Matthias
M
Leippe
Roland
R
Leclercq
Claire
C
Laugier
Joachim
J
Grötzinger
Julien
J
Cauchard
D000193:Actinomycetales Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000662:veterinary; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D005260:Female; D006461:Hemolysis; D006734:Horse Diseases / Q000188:drug therapy* / Q000382:microbiology*; D006736:Horses; D008081:Liposomes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010743:Phospholipids / Q000737:chemistry; D016929:Rhodococcus equi / Q000187:drug effects / Q000648:ultrastructure; D055049:Salt Tolerance; D012756:Sheep; D014709:Vero Cells; D023084:alpha-Defensins / Q000737:chemistry / Q000494:pharmacology*; D001798:Blood Proteins; D011498:Protein Precursors
D000900:Anti-Bacterial Agents; D008081:Liposomes; D010743:Phospholipids; D023084:alpha-Defensins; C573013:DEFA1 protein, equine; C121626:cathelicidin 3 protein, Equus caballus; D001798:Blood Proteins; D011498:Protein Precursors