Metabolic mechanism of ceftazidime resistance in .

BACKGROUND

Microbial metabolism confounds antibiotic efficacy. However, information regarding effect of metabolism on cephalosporin antibiotics-mediated killing and is largely absence, although the drugs are widely used in clinic and the bacteria are pathogens to both human and aquaculture animals.

PURPOSE

This study explores the metabolome of cephalosporin antibiotic-resistant and analyzes the role of bacterial metabolism in drug and multidrug-resistance.

RESULTS

The metabolomes of isogenic ceftazidime-resistant (VA-R) and ceftazidime-sensitive (VA-S) were analyzed using gas chromatography -mass spectrometry. The metabolome of VA-R is characterized by inefficient respiration, an inefficient pyruvate cycle (P cycle), increased biosynthesis of fatty acids and decreased membrane proton motive force. This hypothesis was confirmed by the fact that furfural and malonate, inhibitors of pyruvate dehydrogenase and succinate dehydrogenase (P cycle enzymes), respectively, increased resistance of VA-R to antibiotics, while exposure to triclosan, to inhibit biosynthesis of fatty acids, decreased resistance.

CONCLUSION

These results contribute to our understanding of mechanisms of bacterial antibiotic-resistance and may lead to more effective approaches to treat, manage or prevent infections caused by antibiotic-resistant pathogens including those of the species.