scholarly journals The Cation Diffusion Facilitator Family Protein EmfA Confers Resistance to Manganese Toxicity in Brucella abortus 2308 and Is an Essential Virulence Determinant in Mice

2019 ◽  
Vol 202 (1) ◽  
Author(s):  
Matthew J. Johnsrude ◽  
Joshua E. Pitzer ◽  
Daniel W. Martin ◽  
R. Martin Roop
Keyword(s):  
Brucella Abortus ◽  
Manganese Toxicity ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
Mn Toxicity ◽  
Virulence Determinant ◽  
Family Protein ◽  
Cellular Components ◽  
Cation Diffusion Facilitator Family

Mn nutrition is essential for the basic physiology and virulence of Brucella strains. The results of the study presented here demonstrate that the cation diffusion facilitator (CDF)-type metal exporter EmfA plays critical roles in maintaining Mn homeostasis and preventing Mn toxicity in Brucella and is an essential virulence determinant for these bacteria. EmfA and other cellular components involved in Mn homeostasis represent attractive targets for the development of improved vaccines and chemotherapeutic strategies for preventing and treating brucellosis in humans and animals.

Crystal structure of the cytosolic domain of the cation diffusion facilitator family protein

2009 ◽  
Vol 76 (3) ◽  
pp. 768-771 ◽  
Author(s):  
Takashi Higuchi ◽  
Motoyuki Hattori ◽  
Yoshiki Tanaka ◽  
Ryuichiro Ishitani ◽  
Osamu Nureki
Keyword(s):  
Crystal Structure ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
Family Protein ◽  
Cytosolic Domain ◽  
Cation Diffusion Facilitator Family

ZnT-1 extrudes zinc from mammalian cells functioning as a Zn2+/H+exchanger

Metallomics ◽  
2014 ◽  
Vol 6 (9) ◽  
pp. 1656-1663 ◽  
Author(s):  
Eden Shusterman ◽  
Ofer Beharier ◽  
Levy Shiri ◽  
Raz Zarivach ◽  
Yoram Etzion ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
Mammalian Cells ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
Family Protein

ZnT-1 is a Cation Diffusion Facilitator (CDF) family protein, and is present throughout the phylogenetic tree from bacteria to humans.

scholarly journals Manganese Detoxification by MntE Is Critical for Resistance to Oxidative Stress and Virulence of Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline M. Grunenwald ◽  
Jacob E. Choby ◽  
Lillian J. Juttukonda ◽  
William N. Beavers ◽  
Andy Weiss ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Efflux Pump ◽  
Uptake System ◽  
Cation Diffusion ◽  
Intracellular Iron ◽  
Cation Diffusion Facilitator ◽  
Mn Toxicity ◽  
Content Type

ABSTRACT Manganese (Mn) is an essential micronutrient critical for the pathogenesis of Staphylococcus aureus, a significant cause of human morbidity and mortality. Paradoxically, excess Mn is toxic; therefore, maintenance of intracellular Mn homeostasis is required for survival. Here we describe a Mn exporter in S. aureus, MntE, which is a member of the cation diffusion facilitator (CDF) protein family and conserved among Gram-positive pathogens. Upregulation of mntE transcription in response to excess Mn is dependent on the presence of MntR, a transcriptional repressor of the mntABC Mn uptake system. Inactivation of mntE or mntR leads to reduced growth in media supplemented with Mn, demonstrating MntE is required for detoxification of excess Mn. Inactivation of mntE results in elevated levels of intracellular Mn, but reduced intracellular iron (Fe) levels, supporting the hypothesis that MntE functions as a Mn efflux pump and Mn efflux influences Fe homeostasis. Strains inactivated for mntE are more sensitive to the oxidants NaOCl and paraquat, indicating Mn homeostasis is critical for resisting oxidative stress. Furthermore, mntE and mntR are required for full virulence of S. aureus during infection, suggesting S. aureus experiences Mn toxicity in vivo. Combined, these data support a model in which MntR controls Mn homeostasis by balancing transcriptional repression of mntABC and induction of mntE, both of which are critical for S. aureus pathogenesis. Thus, Mn efflux contributes to bacterial survival and virulence during infection, establishing MntE as a potential antimicrobial target and expanding our understanding of Mn homeostasis. IMPORTANCE Manganese (Mn) is generally viewed as a critical nutrient that is beneficial to pathogenic bacteria due to its function as an enzymatic cofactor and its capability of acting as an antioxidant; yet paradoxically, high concentrations of this transition metal can be toxic. In this work, we demonstrate Staphylococcus aureus utilizes the cation diffusion facilitator (CDF) family protein MntE to alleviate Mn toxicity through efflux of excess Mn. Inactivation of mntE leads to a significant reduction in S. aureus resistance to oxidative stress and S. aureus-mediated mortality within a mouse model of systemic infection. These results highlight the importance of MntE-mediated Mn detoxification in intracellular Mn homeostasis, resistance to oxidative stress, and S. aureus virulence. Therefore, this establishes MntE as a potential target for development of anti-S. aureus therapeutics.

scholarly journals Mn tolerance in rice is mediated by MTP8.1, a member of the cation diffusion facilitator family

2013 ◽  
Vol 64 (14) ◽  
pp. 4375-4387 ◽  
Author(s):  
Zonghui Chen ◽  
Yumi Fujii ◽  
Naoki Yamaji ◽  
Sakine Masuda ◽  
Yuma Takemoto ◽  
...  
Keyword(s):  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
Cation Diffusion Facilitator Family

scholarly journals Genes Encoding Proteins of the Cation Diffusion Facilitator Family That Confer Manganese Tolerance

2003 ◽  
Vol 15 (5) ◽  
pp. 1131-1142 ◽  
Author(s):  
Emmanuel Delhaize ◽  
Tatsuhiko Kataoka ◽  
Diane M. Hebb ◽  
Rosemary G. White ◽  
Peter R. Ryan
Keyword(s):  
Cation Diffusion ◽  
Cation Diffusion Facilitator ◽  
Manganese Tolerance ◽  
Genes Encoding ◽  
Cation Diffusion Facilitator Family
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