Mechanisms of Bacteroides fragilis resistance to metronidazole

Ghotaslou, Reza; Baghi, Hossein Bannazadeh; Alizadeh, Naser; Yekani, Mina; Arbabi, Shahram; Memar, Mohammad Yousef

doi:10.1016/j.meegid.2018.06.020

Cited by 45 publications

(19 citation statements)

References 84 publications

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“…This bacterium constitutes around 1 to 2% of the gut microbiota and approximately 30% of the anaerobic organisms cultured from human feces. It is considered as the most frequent anaerobic pathogen capable of infecting soft tissues and an important etiological agent of diarrhea (67). The genome of B. fragilis virulent strains contains a pathogenic island that encodes a B. fragilis toxin (BFT), which is a heat-labile metalloprotease.…”

Section: Bacteroides Fragilis: Targeting β-Catenin From the Adherens mentioning

confidence: 99%

Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria

2019

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The Wnt/β-catenin signaling pathway is crucial to regulate cell proliferation and polarity, cell determination, and tissue homeostasis. The activation of Wnt/β-catenin signaling is based on the interaction between Wnt glycoproteins and seven transmembrane receptors—Frizzled (Fzd). This binding promotes recruitment of the scaffolding protein Disheveled (Dvl), which results in the phosphorylation of the co-receptor LRP5/6. The resultant molecular complex Wnt–Fzd–LRP5/6-Dvl forms a structural region for Axin interaction that disrupts Axin-mediated phosphorylation/degradation of the transcriptional co-activator β-catenin, thereby allowing it to stabilize and accumulate in the nucleus where it activates the expression of Wnt-dependent genes. Due to the prominent physiological function, the Wnt/β-catenin signaling must be strictly controlled because its dysregulation, which is caused by different stimuli, may lead to alterations in cell proliferation, apoptosis, and inflammation-associated cancer. The virulence factors from pathogenic bacteria such as Salmonella enterica sv Typhimurium, Helicobacter pylori, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Citrobacter rodentium, Clostridium difficile, Bacteroides fragilis, Escherichia coli, Haemophilus parasuis, Lawsonia intracellularis, Shigella dysenteriae, and Staphylococcus epidermidis employ a variety of molecular strategies to alter the appropriate functioning of diverse signaling pathways. Among these, Wnt/β-catenin has recently emerged as an important target of several virulence factors produced by bacteria. The mechanisms used by these factors to interfere with the activity of Wnt/β-catenin is diverse and include the repression of Wnt inhibitors' expression by the epigenetic modification of histones, blocking Wnt–Fzd ligand binding, activation or inhibition of β-catenin nuclear translocation, down- or up-regulation of Wnt family members, and inhibition of Axin-1 expression that promotes β-catenin activity. Such a variety of mechanisms illustrate an evolutionary co-adaptation of eukaryotic molecular signaling to a battery of soluble or structural components synthesized by pathogenic bacteria. This review gathers the recent efforts to elucidate the mechanistic details through which bacterial virulence factors modulate Wnt/β-catenin signaling and its physiological consequences concerning the inflammatory response and cancer.

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Section: Bacteroides Fragilis: Targeting β-Catenin From the Adherens mentioning

confidence: 99%

Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria

2019

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“…Several studies have shown that nitroimidazole reductase (nim) genes may be found in approximately 2% of Bacteroides fragilis [23][24][25]. It appears that a range of mechanisms may confer resistance [23], but none as well established or widespread as the more familiar mobile β-lactam resistance genes of the Enterobacteriaceae have emerged. However, metronidazole resistance levels overall remain relatively low.…”

Section: Discussionmentioning

confidence: 99%

Metronidazole in the Management of Post-Open Haemorrhoidectomy Pain: Systematic Review

Toh

Iredell

et al. 2020

Ann Coloproctol

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ReviewAnn Coloproctol 2020;36(1):5-11 https://doi.org/10. 3393/ac.2020.01.08 Purpose: Open haemorrhoidectomy is associated with significant postoperative pain. Metronidazole is commonly prescribed in the postoperative period as an adjunct to analgesia in pain management. Methods: In our systematic review, studies were identified using PubMed/MEDLINE, Embase/Ovid and Cochrane Register of Controlled Trials databases. Studies were included if they were randomised controlled trials (RCTs) involving interventions with oral metronidazole at any dose over any time period. The primary outcome was pain score (visual analogue scale, VAS) after open haemorrhoidectomy. Secondary outcomes included time to return to normal daily activities, additional analgesia usage, and postoperative complications. Results: Of 14 RCTs reviewed, 4 met inclusion criteria and were selected. The studies comprised 336 study subjects and 169 subjects were randomised to metronidazole while 167 were in the control group. There was a significant reduction in VAS across all time points, with maximal reduction seen on day 5 posthaemorrhoidectomy (mean difference, -2.28; 95% confidence interval, -2.49 to -2.08; P < 0.001). There was no difference in incidence of complications (P = 0.13). The Cochrane Risk of Bias Tool showed 3 of 4 of the studies had a risk of bias. Conclusion: Metronidazole may be associated with decreased pain but there is insufficient evidence from RCTs to provide a strong grade of recommendation. Further RCTs are required.

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“…Metronidazole can inhibit nucleic acid synthesis when it is reduced by disrupting DNA [45]. e reduction of metronidazole often occurs in anaerobic bacteria, and metronidazole is more effective against anaerobic organisms such as Fusobacterium, Bacteroides, Clostridium, Prevotella, and Peptostreptococcus species [46,47]. Metronidazole is available as a cream for the mouth and has a wide spectrum of bactericidal action against oral obligate anaerobes, even against isolates from infected necrotic pulps [48,49].…”

Section: Metronidazolementioning

confidence: 99%

Application of Antibiotics/Antimicrobial Agents on Dental Caries

Qiu

Zhou

et al. 2020

BioMed Research International

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Dental caries is the most common oral disease. The bacteriological aetiology of dental caries promotes the use of antibiotics or antimicrobial agents to prevent this type of oral infectious disease. Antibiotics have been developed for more than 80 years since Fleming discovered penicillin in 1928, and systemic antibiotics have been used to treat dental caries for a long time. However, new types of antimicrobial agents have been developed to fight against dental caries. The purpose of this review is to focus on the application of systemic antibiotics and other antimicrobial agents with respect to their clinical use to date, including the history of their development, and their side effects, uses, structure types, and molecular mechanisms to promote a better understanding of the importance of microbial interactions in dental plaque and combinational treatments.

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Mechanisms of Bacteroides fragilis resistance to metronidazole

Cited by 45 publications

References 84 publications

Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria

Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria

Metronidazole in the Management of Post-Open Haemorrhoidectomy Pain: Systematic Review

Application of Antibiotics/Antimicrobial Agents on Dental Caries

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