TY - JOUR
T1 - XA bacterial virulence protein promotes pathogenicity by inhibiting the Bacterium's Own F1Fo ATP synthase
AU - Lee, Eun Jin
AU - Pontes, Mauricio H.
AU - Groisman, Eduardo A.
N1 - Funding Information:
We thank Dr. Xuanlin Tu for the crosslinking experiments, Dr. John Walker and Dr. Gregory Cook for comments on the manuscript, and anonymous reviewers for valuable suggestions. This work was supported, in part, by grant AI49561 from the National Institutes of Health to E.A.G., who is an investigator of the Howard Hughes Medical Institute.
PY - 2013/7/3
Y1 - 2013/7/3
N2 - Several intracellular pathogens, including Salmonella enterica and Mycobacterium tuberculosis, require the virulence protein MgtC to survive within macrophages and to cause a lethal infection in mice. We now report that, unlike secreted virulence factors that target the host vacuolar ATPase to withstand phagosomal acidity, the MgtC protein acts on Salmonella's own F 1Fo ATP synthase. This complex couples proton translocation to ATP synthesis/hydrolysis and is required for virulence. We establish that MgtC interacts with the a subunit of the F1F o ATP synthase, hindering ATP-driven proton translocation and NADH-driven ATP synthesis in inverted vesicles. An mgtC null mutant displays heightened ATP levels and an acidic cytoplasm, whereas mgtC overexpression decreases ATP levels. A single amino acid substitution in MgtC that prevents binding to the F1Fo ATP synthase abolishes control of ATP levels and attenuates pathogenicity. MgtC provides a singular example of a virulence protein that promotes pathogenicity by interfering with another virulence protein.
AB - Several intracellular pathogens, including Salmonella enterica and Mycobacterium tuberculosis, require the virulence protein MgtC to survive within macrophages and to cause a lethal infection in mice. We now report that, unlike secreted virulence factors that target the host vacuolar ATPase to withstand phagosomal acidity, the MgtC protein acts on Salmonella's own F 1Fo ATP synthase. This complex couples proton translocation to ATP synthesis/hydrolysis and is required for virulence. We establish that MgtC interacts with the a subunit of the F1F o ATP synthase, hindering ATP-driven proton translocation and NADH-driven ATP synthesis in inverted vesicles. An mgtC null mutant displays heightened ATP levels and an acidic cytoplasm, whereas mgtC overexpression decreases ATP levels. A single amino acid substitution in MgtC that prevents binding to the F1Fo ATP synthase abolishes control of ATP levels and attenuates pathogenicity. MgtC provides a singular example of a virulence protein that promotes pathogenicity by interfering with another virulence protein.
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U2 - 10.1016/j.cell.2013.06.004
DO - 10.1016/j.cell.2013.06.004
M3 - Article
C2 - 23827679
AN - SCOPUS:84879919792
SN - 0092-8674
VL - 154
SP - 146
JO - Cell
JF - Cell
IS - 1
ER -