Efficacy of microcin J25 in biomatrices and in a mouse model of Salmonella infection.
OBJECTIVE
To study the possible therapeutic utility of microcin J25 (MccJ25), a peptide RNA polymerase inhibitor.


METHODS
We subjected the antibiotic to two types of assays. First, with an ex vivo assay, we evaluated the stability and efficacy of MccJ25 in complex fluid biomatrices such as human whole blood, plasma and serum, compared with that in conventional laboratory media. Antimicrobial efficacy of MccJ25 was assessed by quantitative culture 2 h after inoculation of the biomatrices with a Salmonella Newport target organism and compared with that of MccJ25-free controls. Second, the antibiotic was tested in a mouse model of Salmonella infection. The latter was induced by intraperitoneal inoculation of 10(6) cfu of Salmonella Newport and the treatment with MccJ25 was initiated at 2 h post-infection.


RESULTS
MccJ25 retained full activity after 24 h of incubation in whole blood, plasma or serum. In addition, it did not show any haemolytic activity. In whole blood, homologous plasma and serum, introduction of MccJ25 was associated with a significant reduction in cfu versus the respective peptide-free controls. The counts of viable bacteria in the spleen and liver of mice treated with MccJ25 at a total dosage of 3 mg/mouse during either 24 h (0.5 mg/mouse every 4 h) or 6 days (0.5 mg/mouse every 24 h) significantly decreased by two or three orders of magnitude (P <or= 0.05) compared with those in control mice.


CONCLUSIONS
Collectively, these findings indicate that the biological activity of MccJ25 is not affected in complex biological matrices. The potent in vitro activity of MccJ25 against Salmonella translates into good in vivo efficacy in a mouse infection model.
Lopez
Fabian E
FE
Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Tucumán), Chacabuco 461, 4000 San Miguel de Tucumán, Tucumán, Argentina.
Vincent
Paula A
PA
Zenoff
Ana M
AM
Salomón
Raúl A
RA
Farías
Ricardo N
RN
D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001430:Bacteriocins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000382:microbiology; D051379:Mice; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology; D013154:Spleen / Q000382:microbiology
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C020411:microcin; D000667:Ampicillin