Physical Characterization of the Manganese-Sensing Pneumococcal Surface Antigen Repressor from <i>Streptococcus pneumoniae</i>

Lisher, John P.; Higgins, Khadine A.; Maroney, Michael J.; Giedroc, David P.

doi:10.1021/bi401132w

Cited by 42 publications

(49 citation statements)

References 72 publications

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“…ScaR represses the expression of scaCBA in the presence of Mn 2ϩ . Biochemical studies of the S. gordonii and S. pneumoniae ScaR proteins have shown that ScaR is a homodimer and contains two metal-binding sites per protomer (85,86). In S. pneumoniae ScaR, Zn 2ϩ occupies site 1, and although it is required for activation, it keeps ScaR in an inactive state.…”

Section: One-component Systemsmentioning

confidence: 99%

“…In S. pneumoniae ScaR, Zn 2ϩ occupies site 1, and although it is required for activation, it keeps ScaR in an inactive state. Activation of DNA-binding activity is accomplished only when Mn 2ϩ occupies the lower-affinity site 2 (85). Zn 2ϩ can also bind to site 2, resulting in ScaR having a low DNA-binding activity (85).…”

Section: One-component Systemsmentioning

confidence: 99%

“…Activation of DNA-binding activity is accomplished only when Mn 2ϩ occupies the lower-affinity site 2 (85). Zn 2ϩ can also bind to site 2, resulting in ScaR having a low DNA-binding activity (85). This effect may partly explain the increase of expression of scaCBA in the presence of toxic levels of Zn 2ϩ (85) (88).…”

Section: One-component Systemsmentioning

confidence: 99%

“…Zn 2ϩ can also bind to site 2, resulting in ScaR having a low DNA-binding activity (85). This effect may partly explain the increase of expression of scaCBA in the presence of toxic levels of Zn 2ϩ (85) (88). Later studies showed that SloR controls a large regulon, acting both as a repressor and as an activator (69,89).…”

Section: One-component Systemsmentioning

confidence: 99%

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Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

541

404

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SUMMARYLactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g.,Lactococcus lactis), probiotic (e.g., severalLactobacillusspp.), and pathogenic (e.g.,EnterococcusandStreptococcusspp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the “stressome” of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.

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Section: One-component Systemsmentioning

confidence: 99%

Section: One-component Systemsmentioning

confidence: 99%

Section: One-component Systemsmentioning

confidence: 99%

Section: One-component Systemsmentioning

confidence: 99%

See 2 more Smart Citations

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

541

404

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“…Excess iron (Fe) is harmful due to its participation in Fenton chemistry, which produces a highly reactive hydroxyl radical that can damage biomolecules (4-7). Other transition metals, including Mn, Zn, cobalt (Co), nickel (Ni), and copper (Cu), become toxic at high concentrations partly because they compete for each other's cognate metal-binding sites in enzymes (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Regardless of the mechanism of metal toxicity, bacteria have evolved ways to minimize the deleterious impact of metal ion excess.…”

mentioning

confidence: 99%

Functional Determinants of Metal Ion Transport and Selectivity in Paralogous Cation Diffusion Facilitator Transporters CzcD and MntE in Streptococcus pneumoniae

Martin

Giedroc

2016

J Bacteriol

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Cation diffusion facilitators (CDFs) are a large family of divalent metal transporters that collectively possess broad metal specificity and contribute to intracellular metal homeostasis and virulence in bacterial pathogens. Streptococcus pneumoniae expresses two homologous CDF efflux transporters, MntE and CzcD. Cells lacking mntE or czcD are sensitive to manganese (Mn) or zinc (Zn) toxicity, respectively, and specifically accumulate Mn or Zn, respectively, thus suggesting that MntE selectively transports Mn, while CzcD transports Zn. Here, we probe the origin of this metal specificity using a phenotypic growth analysis of pneumococcal variants. Structural homology to Escherichia coli YiiP predicts that both MntE and CzcD are dimeric and each protomer harbors four pairs of conserved metal-binding sites, termed the A site, the B site, and the C1/C2 binuclear site. We find that single amino acid mutations within both the transmembrane domain A site and the B site in both CDFs result in a cellular metal sensitivity similar to that of the corresponding null mutants. However, multiple mutations in the predicted cytoplasmic C1/C2 cluster of MntE have no impact on cellular Mn resistance, in contrast to the analogous substitutions in CzcD, which do have on impact on cellular Zn resistance. Deletion of the MntE-specific C-terminal tail, present only in Mn-specific bacterial CDFs, resulted in only a modest growth phenotype. Further analysis of MntE-CzcD functional chimeric transporters showed that Asn and Asp in the ND-DD A-site motif of MntE and the most N-terminal His in the HD-HD site A of CzcD (the specified amino acids are underlined) play key roles in transporter metal selectivity. IMPORTANCECation diffusion facilitator (CDF) proteins are divalent metal ion transporters that are conserved in organisms ranging from bacteria to humans and that play important roles in cellular physiology, from metal homeostasis and resistance to type I diabetes in vertebrates. The respiratory pathogen Streptococcus pneumoniae expresses two metal CDF transporters, CzcD and MntE. How CDFs achieve metal selectivity is unclear. We show here that CzcD and MntE are true paralogs, as CzcD transports zinc, while MntE selectively transports manganese. Through the use of an extensive collection of pneumococcal variants, we show that a primary determinant for metal selectivity is the A site within the transmembrane domain. This extends our understanding of how CDFs discriminate among transition metals. T ransition metals from manganese (Mn) to zinc (Zn) in the first row of the periodic table serve as essential cofactors in metalloenzymes that are required for many important cellular processes, including replication, regulation, and central metabolism, among all domains of life (1-3). Despite their importance, excess transition metals can impair bacterial growth. Excess iron (Fe) is harmful due to its participation in Fenton chemistry, which produces a highly reactive hydroxyl radical that can damage biomolecules (4-7). Other transition m...

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