Inhibition of chlamydial infection in the genital tract of female mice by topical application of a peptide deformylase inhibitor.
Chlamydia trachomatis is an obligate intracellular bacterium responsible for a number of health problems, including sexually transmitted infection in humans. We recently discovered that C. trachomatis infection in cell culture is highly susceptible to inhibitors of peptide deformylase, an enzyme that removes the N-formyl group from newly synthesized polypeptides. In this study, one of the deformylase inhibitors, GM6001, was tested for potential antichlamydial activity using a murine genital C. muridarum infection model. Topical application of GM6001 significantly reduced C. muridarum loading in BALB/c mice that were vaginally infected with the pathogen. In striking contrast, growth of the probiotic Lactobacillus plantarum is strongly resistant to the PDF inhibitor. GM6001 demonstrated no detectable toxicity against host cells. On the basis of these data and our previous observations, we conclude that further evaluation of PDF inhibitors for prevention and treatment of sexually transmitted chlamydial infection is warranted.
Balakrishnan
Amit
A
University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Wang
Lingling
L
Li
Xiaojin
X
Ohman-Strickland
Pamela
P
Malatesta
Paul
P
Fan
Huizhou
H
D000287:Administration, Topical; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D002692:Chlamydia trachomatis / Q000187:drug effects*; D015169:Colony Count, Microbial; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D048191:Lactiplantibacillus plantarum / Q000187:drug effects; D008219:Lymphogranuloma Venereum / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014621:Vagina / Q000382:microbiology
D004151:Dipeptides; D004791:Enzyme Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D000581:Amidohydrolases; C084507:peptide deformylase