Pomares María Fernanda, Vincent Paula A, Farías Ricardo N, Salomón Raúl A
Departamento de Bioquímica de la Nutrición, INSIBIO (Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional de Tucumán), Chacabuco 461, 4000 San Miguel de Tucumán, Argentina.
J Bacteriol. 2008 Jun;190(12):4328-34. doi: 10.1128/JB.00183-08. Epub 2008 Apr 11.
As Escherichia coli strains enter the stationary phase of growth they become more resistant to the peptide antibiotic microcin J25. It is known that starvation for nutrients such as amino acids or glucose leads to increases in guanosine 3',5'-bispyrophosphate (ppGpp) levels and that the intracellular concentration of this nucleotide increases as cells enter the stationary phase of growth. Therefore, we examined the effects of artificially manipulating the ppGpp levels on sensitivity to microcin J25. A direct correlation was found between ppGpp accumulation and microcin resistance. Our results indicate that the nucleotide is required to induce production of YojI, a chromosomally encoded efflux pump which, in turn, expels microcin from cells. This would maintain the intracellular level of the antibiotic below a toxic level.
随着大肠杆菌菌株进入生长稳定期，它们对肽抗生素微菌素J25的抗性增强。已知氨基酸或葡萄糖等营养物质的饥饿会导致鸟苷3',5'-双焦磷酸（ppGpp）水平升高，并且随着细胞进入生长稳定期，这种核苷酸的细胞内浓度会增加。因此，我们研究了人为操纵ppGpp水平对微菌素J25敏感性的影响。发现ppGpp积累与微菌素抗性之间存在直接相关性。我们的结果表明，这种核苷酸是诱导YojI产生所必需的，YojI是一种染色体编码的外排泵，反过来又将微菌素从细胞中排出。这将使抗生素的细胞内水平维持在毒性水平以下。
