Antiangiogenic effect of erythromycin: an in vitro model of Bartonella quintana infection.
BACKGROUND
Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis.


METHODS
The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates.


RESULTS
We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin.


CONCLUSIONS
The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.
Meghari
Soraya
S
Unite des Rickettsies, CNRS UMR 6020, Universite de la Mediterranee, IFR 48, Faculte de Medecine, Marseille, France.
Rolain
Jean-Marc
JM
Grau
Georges E
GE
Platt
Esther
E
Barrassi
Lina
L
Mege
Jean-Louis
JL
Raoult
Didier
D
D000595:Amino Acid Sequence; D016917:Angiomatosis, Bacillary / Q000188:drug therapy* / Q000382:microbiology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018413:Bartonella quintana / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D049109:Cell Proliferation / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D004917:Erythromycin