The CDF-type metal efflux protein EmfA is essential for Brucella abortus 2308 resistance to manganese toxicity and is a critical virulence determinant in experimentally-infected mice

Abstract

Divalent cationic metals are important trace nutrients for all bacteria because metals serve as cofactors for proteins involved in numerous cellular functions. Despite the fact that metals play an essential role in bacterial physiology, metals become harmful to bacteria if accumulated in excess. To prevent metal-induced toxicity, bacteria employ a variety of factors, such as metal-responsive transcriptional regulators and metal efflux proteins, that function to maintain proper intracellular metal homeostasis. The Brucella strains are Gram-negative, pathogenic bacteria that cause the severe febrile zoonotic disease, brucellosis, and these bacteria require the metal manganese for growth and during host infection. While the manganese acquisition protein, MntH, is essential for the capacity of Brucella spp. to maintain sufficient manganese nutrition, the mechanisms by which these bacteria prevent manganese toxicity have not been determined. The studies of this thesis were performed to identify how Brucella spp. cope with manganese toxicity and whether these factors are essential for Brucella virulence.