A Bacterial Virulence Protein Promotes Pathogenicity by Inhibiting the Bacterium’s Own F1Fo ATP Synthase

Lee, Eun Jin; Pontes, Mauricio H.; Groisman, Eduardo A.

doi:10.1016/j.cell.2013.06.004

Cited by 129 publications

(222 citation statements)

References 44 publications

(71 reference statements)

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“…The mgtC gene specifies an inhibitor of the F 1 F o ATPase (25) and may also promote motility by allowing pagM expression given that MgtC controls ATP levels and cytosolic pH (25). In agreement with this notion, the mRNA levels of the pagM gene were fivefold higher in the wild-type strain than in the isogenic mgtC mutant following growth in low Mg 2+ media for 4.5 h ( Fig.…”

Section: Resultssupporting

confidence: 74%

“…And second, pagM transcription requires the Mg 2+ transporter MgtA and the F 1 F o ATPase inhibitor MgtC. This makes PagM-mediated motility contingent on the cytosolic conditions that promote transcription elongation into the mgtA and mgtC coding regions: a decrease in Mg 2+ (18) and an increase in ATP (25), respectively. These cytosolic conditions may be indicative of a need to explore other locales.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Flagella-independent surface motility in Salmonella enterica serovar Typhimurium

Park

Pontes

Groisman

2015

Proc. Natl. Acad. Sci. U.S.A.

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Flagella are multiprotein complexes necessary for swimming and swarming motility. In Salmonella enterica serovar Typhimurium, flagella-mediated motility is repressed by the PhoP/PhoQ regulatory system. We now report that Salmonella can move on 0.3% agarose media in a flagella-independent manner when experiencing the PhoP/PhoQ-inducing signal low Mg 2+ . This motility requires the PhoP-activated mgtA, mgtC, and pagM genes, which specify a Mg 2+ transporter, an inhibitor of Salmonella's own F 1 F o ATPase, and a small protein of unknown function, respectively. The MgtA and MgtC proteins are necessary for pagM expression because pagM mRNA levels were lower in mgtA and mgtC mutants than in wild-type Salmonella, and also because pagM expression from a heterologous promoter rescued motility in mgtA and mgtC mutants. PagM promotes group motility by a surface protein(s), as a pagM-expressing strain conferred motility upon a pagM null mutant, and proteinase K treatment eliminated motility. The pagM gene is rarely found outside subspecies I of S. enterica and often present in nonfunctional allelic forms in organisms lacking the identified motility. Deletion of the pagM gene reduced bacterial replication on 0.3% agarose low Mg 2+ media but not in low Mg 2+ liquid media. Our findings define a form of motility that allows Salmonella to scavenge nutrients and to escape toxic compounds in low Mg 2+ semisolid environments.

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Section: Resultssupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Flagella-independent surface motility in Salmonella enterica serovar Typhimurium

Park

Pontes

Groisman

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…A recent publication has demonstrated a direct interaction between MgtC proteins and subunits of F 1 F o ATP synthase, which results in a biologically important inhibition of ATP synthase function (43). Interestingly, the mgtC gene is also known to be under the control of magnesium-responsive regulation and assists survival under low-magnesium conditions (8,44).…”

Section: Resultsmentioning

confidence: 99%

Assessment of the Requirements for Magnesium Transporters in Bacillus subtilis

et al. 2014

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Magnesium is the most abundant divalent metal in cells and is required for many structural and enzymatic functions. For bacteria, at least three families of proteins function as magnesium transporters. In recent years, it has been shown that a subset of these transport proteins is regulated by magnesium-responsive genetic control elements. In this study, we investigated the cellular requirements for magnesium homeostasis in the model microorganism Bacillus subtilis. Putative magnesium transporter genes were mutationally disrupted, singly and in combination, in order to assess their general importance. Mutation of only one of these genes resulted in strong dependency on supplemental extracellular magnesium. Notably, this transporter gene, mgtE, is known to be under magnesium-responsive genetic regulatory control. This suggests that the identification of magnesium-responsive genetic mechanisms may generally denote primary transport proteins for bacteria. To investigate whether B. subtilis encodes yet additional classes of transport mechanisms, suppressor strains that permitted the growth of a transporter-defective mutant were identified. Several of these strains were sequenced to determine the genetic basis of the suppressor phenotypes. None of these mutations occurred in transport protein homologues; instead, they affected housekeeping functions, such as signal recognition particle components and ATP synthase machinery. From these aggregate data, we speculate that the mgtE protein provides the primary route of magnesium import in B. subtilis and that the other putative transport proteins are likely to be utilized for more-specialized growth conditions.

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“…This appears to be the case for the 296-nt-long leader region of the mgtCBR transcript from Salmonella enterica serovar Typhimurium, which controls transcription elongation into its associated coding region (18,19) but lacks sequences that resemble an intrinsic terminator [i.e., a G + C-rich stem-loop followed by a stretch of Us (12)]. The mgtCBR operon specifies the virulence protein MgtC (20), the Mg 2+ transporter MgtB (21), and the regulatory peptide MgtR (22).…”

mentioning

confidence: 99%

An RNA motif advances transcription by preventing Rho-dependent termination

Sevostyanova

Groisman

2015

Proc. Natl. Acad. Sci. U.S.A.

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The transcription termination factor Rho associates with most nascent bacterial RNAs as they emerge from RNA polymerase. However, pharmacological inhibition of Rho derepresses only a small fraction of these transcripts. What, then, determines the specificity of Rho-dependent transcription termination? We now report the identification of a Rho-antagonizing RNA element (RARE) that hinders Rho-dependent transcription termination. We establish that RARE traps Rho in an inactive complex but does not prevent Rho binding to its recruitment sites. Although translating ribosomes normally block Rho access to an mRNA, inefficient translation of an open reading frame in the leader region of the Salmonella mgtCBR operon actually enables transcription of its associated coding region by favoring an RNA conformation that sequesters RARE. The discovery of an RNA element that inactivates Rho signifies that the specificity of nucleic-acid binding proteins is defined not only by the sequences that recruit these proteins but also by sequences that antagonize their activity.T ranscription factors recognize sequence and structural elements in DNA and RNA to turn genes on or off. The transcription termination factor Rho is responsible for the majority of factor-dependent termination events in enteric bacterial species (1). Rho prevents the production of dysfunctional, and potentially dangerous, RNAs (2). For instance, Rho implements transcriptional polarity, a process whereby compromised translation of a promoter-proximal gene reduces transcription of downstream genes in an operon (3-5).Rho is a hexameric helicase that binds RNA and translocates in the 5′-to-3′ direction using the energy derived from ATP hydrolysis. Initially, RNA is anchored to Rho primary binding sites on the surface of the hexamer. Rho recruitment sites tend to be rich in Cs and Us and free of strong secondary structures (6-8). Interaction with a recruitment site causes the Rho hexamer to open briefly, allowing the RNA 3′ region to pass through the center, where secondary binding sites are located (9, 10). Further contact between the RNA and the secondary binding sites stimulates Rho's ATPase activity (11). Using the energy derived from ATP hydrolysis, Rho translocates along an RNA until it reaches a paused RNA polymerase (RNAP) and promotes transcription termination (12).The specificity of Rho-dependent transcription termination has remained enigmatic because Rho associates with many newly transcribed RNAs in Escherichia coli (13), but only a portion of these messages is affected when bacteria are treated with bicyclomycin (BCM) (1), a Rho-specific inhibitor (14). In other words, binding of Rho to a particular RNA is not sufficient for subsequent transcription termination.Rho-dependent terminators are typically found at the end of operons; however, they can also be present in the leader region of mRNAs, where they perform regulatory functions (15)(16)(17)). This appears to be the case for the 296-nt-long leader region of the mgtCBR transcript from Salmonella enteri...

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A Bacterial Virulence Protein Promotes Pathogenicity by Inhibiting the Bacterium’s Own F1Fo ATP Synthase

Cited by 129 publications

References 44 publications

Flagella-independent surface motility in Salmonella enterica serovar Typhimurium

Flagella-independent surface motility in Salmonella enterica serovar Typhimurium

Assessment of the Requirements for Magnesium Transporters in Bacillus subtilis

An RNA motif advances transcription by preventing Rho-dependent termination

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