Integrated Experimental and Computational Analyses Reveal Differential Metabolic Functionality in Antibiotic-Resistant Pseudomonas aeruginosa.

Metabolic adaptations accompanying the development of antibiotic resistance in bacteria remain poorly understood. To study this relationship, we profiled the growth of lab-evolved antibiotic-resistant lineages of the opportunistic pathogen Pseudomonas aeruginosa across 190 unique carbon sources. Our data revealed that the evolution of antibiotic resistance resulted in systems-level changes to growth dynamics and metabolic phenotype.

History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment.

Antibiotic regimens often include the sequential changing of drugs to limit the development and evolution of resistance of bacterial pathogens. It remains unclear how history of adaptation to one antibiotic can influence the resistance profiles when bacteria subsequently adapt to a different antibiotic. Here, we experimentally evolved Pseudomonas aeruginosa to six 2-drug sequences.

Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis.

Virulence-linked pathways in opportunistic pathogens are putative therapeutic targets that may be associated with less potential for resistance than targets in growth-essential pathways. However, efficacy of virulence-linked targets may be affected by the contribution of virulence-related genes to metabolism. We evaluate the complex interrelationships between growth and virulence-linked pathways using a genome-scale metabolic network reconstruction of Pseudomonas aeruginosa strain PA14 and an updated, expanded reconstruction of P.

Comparative metabolic systems analysis of pathogenic Burkholderia.

Burkholderia cenocepacia and Burkholderia multivorans are opportunistic drug-resistant pathogens that account for the majority of Burkholderia cepacia complex infections in cystic fibrosis patients and also infect other immunocompromised individuals. While they share similar genetic compositions, B. cenocepacia and B.

A two-compartment model of VEGF distribution in the mouse.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis--the growth of new microvessels from existing microvasculature. Angiogenesis is a complex process involving numerous molecular species, and to better understand it, a systems biology approach is necessary. In vivo preclinical experiments in the area of angiogenesis are typically performed in mouse models; this includes drug development targeting VEGF.