Effects of Subminimum Inhibitory Concentrations of Antibiotics on thePasteurellamultocidaProteome

Abstract
Subminimum inhibitory concentrations (sub-MICs) of antibiotics can be therapeutically effective, but the underlying molecular mechanisms are not well-characterized. We analyzed the Pasteurella multocida proteome response to sub-MICs of amoxicillin, chlortetracycline, and enrofloxacin using isotope-coded affinity tags (ICAT). There were parallel effects on inhibition of growth kinetics and suppression of protein expression by clusters of orthologous groups (COG) categories. Potential compensatory mechanisms enabling antibiotic adaptation were identified, including increased RecA expression caused by enrofloxacin. Keywords: isotope-coded affinity tag • ICAT • antibiotic • subminimum inhibitory concentration • enrofloxacin • chlortetracycline • amoxicillin • bovine respiratory disease • clusters of orthologous groups • RecA