Microcin J25 activity in a murine systemic infection model

FABIÁN LÓPEZ, PAULA VINCENT, RAÚL SALOMÓN, RICARDO FARÍAS

Pinamar, Buenos Aires

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología molecular; 2005

SAIB

Microcin J25 (MccJ25) is a plasmid-encoded antibiotic consisting of 21 amino acid residues. This study was performed to determine the MccJ25 activity in an in vivo Salmonella Newport infection model. Two groups of BALB/c mice were inoculated with 106 bacteria. Two hours after infection, one group was treated with MccJ25, whereas the other was kept as a control. Two schemes of MccJ25 treatment were followed: i) Intraperitoneal injection of 18 mg/kg every 24 h during 146 h; and ii) the same dose every 4 hs during 28 h. Upon completion of the treatments, the mice were killed and the livers and spleens were removed to determine the colony forming units (CFU) per organ. The statistical significance of the differences between the numbers of viable organism in the organs of treated and untreated mice was determined. Colony counts decreased significantly (p<0,0001) in livers and spleens of treated group with the two treatments. The pharmacokinetic of MccJ25 was studied to determine the MccJ25 permanence in plasma. The mice were injected with 0,2; 0,5; 1 or 2 mg of antibiotic and blood samples were taken at various times after drug administration (5, 10, 15, 30, 60, 120, 180, and 240 min). MccJ25 reached the maximum concentration in plasma at 30 min. Microcin was still detectable 4 to 6 h after administration, depending of the dose injected. The present results open the way to study in vivo the therapeutic action of MccJ25.