Transcriptional response of Streptococcus pneumoniae to Zn2+ limitation and the repressor/activator function of AdcR

Shafeeq, Sulman; Kloosterman, Tomas G.; Kuipers, Oscar P.

doi:10.1039/c1mt00030f

Cited by 64 publications

(97 citation statements)

References 58 publications

(120 reference statements)

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“…In addition to genes encoding the Adc/Lmb system, we found a perfect AdcR box in the promoter region (400 bp upstream from the start codon) of 7 supplementary genes or operons (Table 3), in particular, upstream of the adh gene (sak_0087), encoding a potential zinc-containing alcohol dehydrogenase, which has already been identified to be a direct binding target of AdcR in S. pneumoniae (26,42).…”

Section: Resultsmentioning

confidence: 85%

“…We have shown that the expression of the lmb, adcA, and adcAII genes is zinc dependent. Zn 2ϩ -dependent regulation is mediated in S. pneumoniae and S. pyogenes by the AdcR regulator (26,27,42). S. pneumoniae AdcR has a unique effector in zinc, and its crystal structure revealed the presence of two metal-binding sites (43).…”

Section: Resultsmentioning

confidence: 99%

“…Zinc-binding proteins in other bacteria are upregulated under zinc limitation (26). We therefore examined lmb-sht expression in the presence of various concentrations of extracellular zinc, using a transcriptional lacZ fusion approach.…”

Section: Resultsmentioning

confidence: 99%

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The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

et al. 2016

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The Lmb protein of Streptococcus agalactiae is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of lmb, adcA, and adcAII, or that of the adcCB genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes S. agalactiae growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in S. agalactiae and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium. IMPORTANCEA zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in Streptococcus agalactiae. This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids. S treptococcus agalactiae (group B streptococcus [GBS]) is aGram-positive commensal bacterium of the human gastrointestinal and uro-genital tracts. GBS carriage is mostly asymptomatic in healthy adults, and this bacterium is detected in the vagina of approximatively 30% of pregnant women. Maternal carriage is the main source of transmission to neonates, in which S. agalactiae can cause invasive infections (pneumonia, septicemia, and meningitis), with an overall mortality rate of approximately 10% (1, 2). GBS is also an emergent pathogen among the elderly and in adults with underlying diseases (1, 3).The ability of GBS to colonize different niches and cause infection is multifactorial, and many virulence-associated proteins have been identified (4, 5). Binding of GBS adhesins to components of the extracellular matrix constitutes a crucial first step in the process of infection (6-9). Among them, the Lmb protein has been identified as a GBS receptor for laminin, a glycosylated multidomain protein found in all human tissues (10). The gene encoding Lmb is located on a transposon with the scpB and sht genes, which encode a C5a peptidase and a histidine triad protein, respectively (11, 12). The lmb promoter region is a hot spot for the integration of two mobile genetic elements. One of them is associated with increased expression of lmb, resulting in increased binding of strains harboring the transposon to laminin (13). It has also been shown that Lmb may promote bacterial invasion in human brain microvascular endothelial cell lines (14).Lmb is clustered by sequence homology as a metal-binding receptor. Indeed, Lmb has strong homology with the zinc-binding proteins AdcA and Lbp of other streptococcal species (15, 16). Th...

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

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The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

et al. 2016

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“…S. pneumoniae encodes a homologous Zn 2ϩ uptake system (AdcABC) that is regulated by a ZitR homolog (AdcR) (76). AdcR also regulates the expression of the four pneumococcal histidine triad (Pht) proteins, PhtA, PhtB, PhtD, and PhtE (77), involved in surface adhesion, as well as the Zn 2ϩ -specific AdcA homolog AdcAII and a Zn 2ϩ -dependent alcohol dehydrogenase (78,79). The adc operon is present in most streptococci and has also been studied in Streptococcus gordonii, where it is involved in Mn 2ϩ homeostasis (80), and in Streptococcus suis, where it regulates the expression of a Zn 2ϩ /Mn 2ϩ uptake system, ribosomal genes, and pht genes (81).…”

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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“…It may act as a structural element, helping to maintain the conformation of particular protein domains, or as a catalytic cofactor in the active site of a variety of enzymes (13). Zinc sensing in bacteria is carried out by regulators of different families, including SmtB/ ArsR, MerR, TetR, MarR, and the Fur family (10,26,32,37,54). Zur (zinc uptake regulator) proteins belong to the Fur family.…”

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confidence: 99%

Characterization of the Response to Zinc Deficiency in the Cyanobacterium Anabaena sp. Strain PCC 7120

Napolitano

Rubio

Santamaría-Gómez

et al. 2012

Journal of Bacteriology

101

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bZur regulators control zinc homeostasis by repressing target genes under zinc-sufficient conditions in a wide variety of bacteria. This paper describes how part of a survey of duplicated genes led to the identification of the open reading frame all2473 as the gene encoding the Zur regulator of the cyanobacterium Anabaena sp. strain PCC 7120. All2473 binds to DNA in a zinc-dependent manner, and its DNA-binding sequence was characterized, which allowed us to determine the relative contribution of particular nucleotides to Zur binding. A zur mutant was found to be impaired in the regulation of zinc homeostasis, showing sensitivity to elevated concentrations of zinc but not other metals. In an effort to characterize the Zur regulon in Anabaena, 23 genes containing upstream putative Zur-binding sequences were identified and found to be regulated by Zur. These genes are organized in six single transcriptional units and six operons, some of them containing multiple Zur-regulated promoters. The identities of genes of the Zur regulon indicate that Anabaena adapts to conditions of zinc deficiency by replacing zinc metalloproteins with paralogues that fulfill the same function but presumably with a lower zinc demand, and with inducing putative metallochaperones and membrane transport systems likely being involved in the scavenging of extracellular zinc, including plasma membrane ABC transport systems and outer membrane TonB-dependent receptors. Among the Zur-regulated genes, the ones showing the highest induction level encode proteins of the outer membrane, suggesting a primary role for components of this cell compartment in the capture of zinc cations from the extracellular medium.

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Transcriptional response of Streptococcus pneumoniae to Zn2+ limitation and the repressor/activator function of AdcR

Cited by 64 publications

References 58 publications

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

Stress Physiology of Lactic Acid Bacteria

Characterization of the Response to Zinc Deficiency in the Cyanobacterium Anabaena sp. Strain PCC 7120

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