The cation diffusion facilitator family protein EmfA confers resistance to manganese toxicity in Brucella abortus 2308 and is an essential virulence determinant in mice

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Matthew Johnsrude (Creator)

Daniel W. Martin (Creator)

Joshua E. Pitzer (Creator)

R. Martin Roop (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Brucella abortus is a Gram-negative bacterium that causes abortion and infertility in food animals and a chronic debilitating febrile disease in humans known as brucellosis. As with all pathogenic bacteria , the Brucella spp. require sufficient metal nutrition during the course of an infection. Host-mediated 'metal withdrawal' defenses actively restrict the bioavailability of metals which requires invading bacteria to employ high affinity metal acquisition systems to overcome these metal-limiting conditions. While obtaining sufficient metals during host infection is critical to the survival of these bacteria , avoiding metal toxicity is equally important. Excess accumulation of one metal relative to others can lead to protein mis-metallation when surplus metal ions outcompete other metal species for their native binding sites. To prevent metal toxicity , bacteria respond to high intracellular metal concentrations by means of metal-responsive transcriptional regulators that downregulate metal import systems , and exporters that remove excess intracellular metal. Manganese (Mn) is an essential micronutrient for Brucella strains , and the purpose of this study was to better define the cellular components that maintain Mn homeostasis and prevent Mn toxicity in these bacteria. The Mn-responsive repressor Mur downregulates the expression of mntH , the gene encoding the sole high affinity Mn importer in Brucella in response to increased intracellular levels of Mn. But phenotypic analysis of a B. abortus mur mutant suggests that Mur plays a minimal role in preventing Mn toxicity. Instead , an ortholog of the cation diffusion facilitator (CDF) type metal exporter EmfA , which prevents Mn toxicity in the close phylogenetic relative Rhizobium etli , is critical for preventing Mn toxicity in Brucella. The experimental findings of this study indicate that EmfA-mediated resistance to Mn toxicity plays a critical role in the virulence of Brucella strains , and suggests that the primary function of EmfA may be to maintain the proper intracellular balance of Mn in these bacteria during the course of infection.

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Johnsrude , M.J.; Pitzer , J.E.; Martin , D.W.; Roop , R.M. , II (2019 , April). The cation diffusion facilitator family protein EmfA confers resistance to manganese toxicity in Brucella abortus 2308 and is an essential virulence determinant in mice. ECU Research and Creative Achievement Week , East Carolina University , Greenville , NC.

Language: English

Date: 2019

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