Antibiotics and Antibiotic Resistance

Biography

Biography: Samir Kumar-Singh

Abstract

P. aeruginosa is a unique organism able to grow in the harshest environments and is characterized by both a large genome as well as unique mechanisms that allow for enhanced genomic and metabolic plasticity making this organism a robust nosocomial pathogen equipped with a myriad of virulence factors as well as antibiotic resistance adaptations. Low-level exposure to antibiotics, both in hospital settings as well as from livestock and wastewater pollution showed that resistance selection and phenotypic alterations could already occur at sub-inhibitory concentrations. Using a multiplex labeling strategy followed by mass spectrometry, we showed a differential response of P. aeruginosa when challenged with sub-inhibitory concentrations of imipenem, colistin, cefepime and tobramycin by both laboratory strains as well as clinical isolates recovered from ventilator-associated pneumonia (VAP) patients. Low-level exposure to imipenem induced expression of AlgR and AlgC proteins that are known to be involved in biofilm formation as well as in regulating virulence and were observed to be most elevated in the laboratory strains. Moreover, Hcp1 and ClpV1, both main components of H1-type-6 secretion system were increased following imipenem exposure in all isolates used. Tobramycin on the other hand induced marked up-regulation of proteins involved in branched amino acid metabolism, electron transport chain proteins and superoxide dismutase indicating that tobramycin induces oxidative stress, a mechanism previously observed with E. coli. Cefepime and colistin only showed a marginal effect on protein expression at sub-inhibitory concentrations. The demonstration of a differential response of P. aeruginosa towards different antibiotic classes at sub-inhibitory concentrations gives us further insights in the potential resistance mechanisms and cellular physiology of this highly pathogenic bacterium and will be the focus of the talk.