A Novel Antimicrobial Approach Based on the Inhibition of Zinc Uptake in
            <i>Salmonella Enterica</i>

Battistoni, Andrea; Ammendola, Serena; Chiancone, Emilia; Ilari, Andrea

doi:10.4155/fmc-2017-0042

Cited by 14 publications

(4 citation statements)

References 42 publications

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“…However, during the early stage of zinc deficiency, gut microbial composition was mildly disrupted, whereas significant functional modifications were indicated by decreased choline demethylation efficiency (Mayneris‐Perxachs, et al , ). Zinc transporters, such as ZnT8 and ZnuABC, are involved in the maintenance of the cellular zinc level, deficiencies in which were reported to reshape the gut microbial pattern (Mao, et al , ) and impact the infectious ability of gut pathogens (Battistoni, et al , ); thus, zinc transporters are new targets for the treatment of metabolic dysfunction or infection‐related comorbidities. Dietary zinc–curcumin supplementation improved the gut dysbiosis associated with zinc dysregulation and the cardiotoxicity induced by doxorubicin in rats (Wu, et al , ), providing a basis for future clinical studies to support the development of novel approaches for cardiotoxicity prevention.…”

Section: Gut Microbiota Interventions For Cvdmentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

128

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Summary The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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Section: Gut Microbiota Interventions For Cvdmentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

128

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“…The outer membrane of Gram-negative bacteria is thought to be permeable to low-molecular-weight hydrophilic molecules and to small ions (Delcour, 2009). Thus, in a zinc-rich environment, zinc ions may passively diffuse from the extracellular space into the periplasm, where the metal is ISSN 2059-7983 bound by specific proteins which mediate its transport across the inner membrane to the cytoplasm (Battistoni et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Structure and metal-binding properties of PA4063, a novel player in periplasmic zinc trafficking byPseudomonas aeruginosa

Fiorillo¹,

Battistoni²,

Ammendola³

et al. 2021

Acta Crystallogr D Struct Biol

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The capability to obtain essential nutrients in hostile environments is a critical skill for pathogens. Under zinc-deficient conditions, Pseudomonas aeruginosa expresses a pool of metal homeostasis control systems that is complex compared with other Gram-negative bacteria and has only been partially characterized. Here, the structure and zinc-binding properties of the protein PA4063, the first component of the PA4063–PA4066 operon, are described. PA4063 has no homologs in other organisms and is characterized by the presence of two histidine-rich sequences. ITC titration detected two zinc-binding sites with micromolar affinity. Crystallographic characterization, performed both with and without zinc, revealed an α/β-sandwich structure that can be classified as a noncanonical ferredoxin-like fold since it differs in size and topology. The histidine-rich stretches located at the N-terminus and between β3 and β4 are disordered in the apo structure, but a few residues become structured in the presence of zinc, contributing to coordination in one of the two sites. The ability to bind two zinc ions at relatively low affinity, the absence of catalytic cavities and the presence of two histidine-rich loops are properties and structural features which suggest that PA4063 might play a role as a periplasmic zinc chaperone or as a concentration sensor useful for optimizing the response of the pathogen to zinc deficiency.

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“…In S. enterica serovar Typhimurium, and other Gram-negative pathogens that infect the gastrointestinal tract, ZnuABC is the only high-affinity zinc transporter present. Deletion of znuA or znuABC in Salmonella causes a growth defect in zinc depleted media compared to wild-type strains [ 35 , 36 ], and the lethal dose of ΔznuABC strains is several orders of magnitude higher than wild-type in a murine model [ 36 ]. This underscores the potential of zinc uptake systems as novel targets for antimicrobial drugs in Gram-negative bacteria generally.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Response of Burkholderia cenocepacia H111 to Severe Zinc Starvation

Barnett

2023

Br J Biomed Sci

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Burkholderia cenocepacia is an opportunistic pathogen that is primarily associated with severe respiratory infections in people with cystic fibrosis. These bacteria have significant intrinsic resistance to antimicrobial therapy, and there is a need for more effective treatments. Bacterial zinc uptake and homeostasis systems are attractive targets for new drugs, yet our understanding of how bacteria acquire and utilise zinc remains incomplete. Here we have used RNA-sequencing and differential gene expression analysis to investigate how B. cenocepacia H111 is able to survive in zinc poor environments, such as those expected to be encountered within the host. The data shows that 201 genes are significantly differentially expressed when zinc supply is severely limited. Included in the 85 upregulated genes, are genes encoding a putative ZnuABC high affinity zinc importer, two TonB-dependent outer membrane receptors that may facilitate zinc uptake across the outer cell membrane, and a COG0523 family zinc metallochaperone. Amongst the 116 downregulated genes, are several zinc-dependent enzymes suggesting a mechanism of zinc sparring to reduce the cells demand for zinc when bioavailability is low.

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A Novel Antimicrobial Approach Based on the Inhibition of Zinc Uptake in Salmonella Enterica

Cited by 14 publications

References 42 publications

The gut microbiota and its interactions with cardiovascular disease

The gut microbiota and its interactions with cardiovascular disease

Structure and metal-binding properties of PA4063, a novel player in periplasmic zinc trafficking byPseudomonas aeruginosa

Transcriptional Response of Burkholderia cenocepacia H111 to Severe Zinc Starvation

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