Comparative Genome-Scale Metabolic Modeling of Metallo-Beta-Lactamase-Producing Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates

The emergence and spread of metallo-beta-lactamase-producing multidrug-resistant (MDR) Klebsiella pneumoniae is a serious public health threat, which is further complicated by the increased prevalence of colistin resistance. The link between antimicrobial resistance acquired by strains of Klebsiella and their unique metabolic capabilities has not been determined. Here, we reconstruct genome-scale metabolic models for 22 K. pneumoniae strains with various resistance profiles to different antibiotics, including two strains exhibiting colistin resistance isolated from Cairo, Egypt. We use the models to predict growth capabilities on 265 different sole carbon, nitrogen, sulfur, and phosphorus sources for all 22 strains. Alternate nitrogen source utilization of glutamate, arginine, histidine, and ethanolamine among others provided discriminatory power for identifying resistance to amikacin, tetracycline, and gentamicin. Thus, genome-scale model based predictions of growth capabilities on alternative substrates may lead to construction of classification trees that are indicative of antibiotic resistance in Klebsiella isolates.