The novel transcriptional regulator SczA mediates protection against Zn2+stress by activation of the Zn2+‐resistance geneczcDinStreptococcus pneumoniae

Kloosterman, Tomas G.; Kooi-Pol, Magdalena M. van der; Bijlsma, Jetta J. E.; Kuipers, Oscar P.

doi:10.1111/j.1365-2958.2007.05849.x

Cited by 117 publications

(176 citation statements)

References 71 publications

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“…Metal analysis demonstrated that total Zn content was increased within activated macrophages infected with the fungal pathogen Histoplasma capsulatum (78). This was the result of increased Zn import via the ZIP2 importer, but the Zn ion was then distributed to intracellular Decreased survival [70] organelles such as the Golgi apparatus via Zn transporters ZnT4 and ZnT7 or bound to metallothionein (78). By contrast, LPS binding to the TLR4 receptor does not trigger Zn import into the macrophage.…”

Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 98%

“…They typically consist of a transcriptional response regulator paired with the Zn efflux transporter, although there may be some redundancies in these exporters. The best exemplified Zn export systems in the literature are the ZntR/ZntA regulator/P-type ATPase Zn efflux system in E. coli (68,69) and the GczA (SczA)/CzcD regulator/cation diffusion facilitator system in S. pyogenes and S. pneumoniae (70,71).…”

Section: The Role Of Bacterial Cu and Zn Detoxification Systems In VImentioning

confidence: 99%

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The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

330

268

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Zinc (Zn) and copper (Cu) are essential for optimal innate immune function, and nutritional deficiency in either metal leads to increased susceptibility to bacterial infection. Recently, the decreased survival of bacterial pathogens with impaired Cu and/or Zn detoxification systems in phagocytes and animal models of infection has been reported. Consequently, a model has emerged in which the host utilizes Cu and/or Zn intoxication to reduce the intracellular survival of pathogens. This review describes and assesses the potential role for Cu and Zn intoxication in innate immune function and their direct bactericidal function.Six first row d-block metal ions, manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and zinc (Zn), are essential micronutrients in living organisms. Investigations and discussions of the roles of these trace metals in biology often relate to their acquisition, storage, and incorporation into enzymes. However, conditions where these metal ions are present in excess or are found in the wrong location, resulting in toxicity, have also been described. Thus, there are also systems that sequester, export, and detoxify excess trace metal ions. Today, the concept of trace metal homeostasis, in which various cellular actions maintain the fine balance between nutrition and toxicity, is well developed.Recently, the concept of "nutritional immunity" has emerged in the context of host defense against pathogens. This envisages a role for mechanisms that protect the host from invading pathogens by restricting their ability to acquire key transition metal ions. One example involves lipocalin, which binds siderophores and thereby prevents Fe acquisition by bacterial pathogens (1). Another is calprotectin, which restricts acquisition of Zn or Mn (2). However, what if the host was able to harness the toxic properties of transition metal ions and use them as bactericides? This review explores the evidence for an antimicrobial role for Cu and Zn in the host defense against bacterial pathogens.

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Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 98%

Section: The Role Of Bacterial Cu and Zn Detoxification Systems In VImentioning

confidence: 99%

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

330

268

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“…Two TFRs, SczA and ComR, bind metals, but the molecular details of these interactions are not known (71,72). Further structural studies will provide clues as to the mechanisms surrounding how TFRs specifically recognize metal ions.…”

Section: Figmentioning

confidence: 99%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

467

512

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SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

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“…A small number of TetR family regulators have been characterized for LAB, among which only S. pneumoniae SczA has so far been implicated in a stress response. Resistance against zinc in S. pneumoniae depends mostly on the CzcD transporter, whose expression is under the control of SczA and whose activity is Zn 2ϩ dependent (82). Despite extensive studies on other TetR regulators, metal-binding TetR regulators are quite uncommon in bacteria and await further characterization (68).…”

Section: One-component Systemsmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

515

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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The novel transcriptional regulator SczA mediates protection against Zn²⁺stress by activation of the Zn²⁺‐resistance geneczcDinStreptococcus pneumoniae

Cited by 117 publications

References 71 publications

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

The TetR Family of Regulators

Stress Physiology of Lactic Acid Bacteria

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