Zinc Level and Its Role in Recurrent <i>Clostridium difficile</i> Infection: A Case Report and Literature Review

Parvataneni, Swetha; Dasari, Avinash R

doi:10.1177/2324709620941315

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…Several lines of evidence suggest dietary Zn 2+ increases the severity and likelihood of CDI 5,39 , but the pleiotropic roles of Zn 2+ have obfuscated the exact mechanism by which it facilitates pathogenesis. Recent studies have found that calprotectin, a protein secreted by the immune system in response to intestinal inflammation, inhibits C. difficile growth 6 .…”

Section: All Classes Of β-Lactam Antibiotics and The Zn 2+ -Chelators...mentioning

confidence: 99%

A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile

et al. 2022

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Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C. difficile has four different PBPs (PBP1-3 and SpoVD) with various roles in growth and spore formation, and their specific links to β-lactam resistance in this pathogen are underexplored. Here, we show that PBP2 (known to be essential for vegetative growth) is the primary bactericidal target for β-lactams in C. difficile. PBP2 is insensitive to cephalosporin inhibition, and this appears to be the main basis for cephalosporin resistance in this organism. We determine crystal structures of C. difficile PBP2, alone and in complex with β-lactams, revealing unique features including ligand-induced conformational changes and an active site Zn2+-binding motif that influences β-lactam binding and protein stability. The Zn2+-binding motif is also present in C. difficile PBP3 and SpoVD (which are known to be essential for sporulation), as well as in other bacterial taxa including species living in extreme environments and the human gut. We speculate that this thiol-containing motif and its cognate Zn2+ might function as a redox sensor to regulate cell wall synthesis for survival in adverse or anaerobic environments.

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Section: All Classes Of β-Lactam Antibiotics and The Zn 2+ -Chelators...mentioning

confidence: 99%

A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile

et al. 2022

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“…Three papers have implicated the importance of zinc in patients with CDI: a case study ( 34 ) and two retrospective cohort studies ( 33 , 35 ), The case report showed the history of a 52-year-old diabetic patient who had undergone kidney transplantation and developed recurrent CDI, presenting with persistent diarrhea and weight loss of 13kg. The initial treatment was with vancomycin.…”

Section: Micronutrientsmentioning

confidence: 99%

“…The patient underwent another cycle of vancomycin, however, in combination with zinc supplementation. Improvement of symptoms, including diarrhea, without a new CDI recurrence episode, was reported ( 34 ).…”

Section: Micronutrientsmentioning

confidence: 99%

Host and Clostridioides difficile-Response Modulated by Micronutrients and Glutamine: An Overview

et al. 2022

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Changes in intestinal microbiota are integral to development of Clostridioides difficile (C. difficile)—associated nosocomial diarrhea. Certain diets, especially Western diets, increase susceptibility to C. difficile infection (CDI). Here, we discuss recent findings regarding how nutrients modulate response of the host and C. difficile during infection. Calcium has a role in the sporulation and germination process. Selenium is effective in reducing the total amount of C. difficile toxin A (TcdA) and toxin B (TcdB) and in decreasing its cytotoxicity. In addition, selenium phosphate synthetase deficiency reduces C. difficile growth and spore production. On the other hand, iron has a dual role in C. difficile growth. For instance, high intracellular levels can generate reactive hydroxyl radicals, whereas low levels can reduce its growth. In humans, zinc deficiency appears to be related to the recurrence of CDI, in contrast, in the CDI model in mice a diet rich in zinc increased the toxin's activity. Low vitamin D levels contribute to C. difficile colonization, toxin production, and inflammation. Furthermore, glutamine appears to protect intestinal epithelial cells from the deleterious effects of TcdA and TcdB. In conclusion, nutrients play an important role in modulating host and pathogen response. However, further studies are needed to better understand the mechanisms and address some controversies.

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“…These findings are indicative of the potential hazards of “free” Zn 2+ upon overexposure, when the number of Zn ions exceed the Zn-binding capacity of the host organism. This hypothesis is indirectly supported by the observation of a significant improvement in symptoms and reduction in the risk of recurrence in Zn-deficient subjects with recurrent C. difficile infection following Zn supplementation [ 63 ].…”

Section: Zn and Microbiota Upon Exposure To Toxic And Infectious Agentsmentioning

confidence: 99%

Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues

Skalny

Aschner

Lei

et al. 2021

IJMS

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The objective of the present study was to review the existing data on the association between Zn status and characteristics of gut microbiota in various organisms and the potential role of Zn-induced microbiota in modulating systemic effects. The existing data demonstrate a tight relationship between Zn metabolism and gut microbiota as demonstrated in Zn deficiency, supplementation, and toxicity studies. Generally, Zn was found to be a significant factor for gut bacteria biodiversity. The effects of physiological and nutritional Zn doses also result in improved gut wall integrity, thus contributing to reduced translocation of bacteria and gut microbiome metabolites into the systemic circulation. In contrast, Zn overexposure induced substantial alterations in gut microbiota. In parallel with intestinal effects, systemic effects of Zn-induced gut microbiota modulation may include systemic inflammation and acute pancreatitis, autism spectrum disorder and attention deficit hyperactivity disorder, as well as fetal alcohol syndrome and obesity. In view of both Zn and gut microbiota, as well as their interaction in the regulation of the physiological functions of the host organism, addressing these targets through the use of Zn-enriched probiotics may be considered an effective strategy for health management.

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Zinc Level and Its Role in Recurrent Clostridium difficile Infection: A Case Report and Literature Review

Cited by 6 publications

References 20 publications

A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile

A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile

Host and Clostridioides difficile-Response Modulated by Micronutrients and Glutamine: An Overview

Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues

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