Antimicrobial resistance in Neisseria gonorrhoeae : history, molecular mechanisms and epidemiological aspects of an emerging global threat

Costa-Lourenço, Ana Paula Ramalho da; Santos, Késia Thaís Barros dos; Moreira, Beatriz Meurer; Fracalanzza, Sérgio Eduardo Longo; Bonelli, Raquel Regina

doi:10.1016/j.bjm.2017.06.001

Cited by 80 publications

(57 citation statements)

References 101 publications

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“…Despite clear activation of recombinant E. coli ClpP in vitro, the imipridones have variable cellular activity against Gram-negative species due to the powerful innate resistance mechanisms in these organisms. Notably though, ONC212 inhibits growth of N. gonorrhoeae, for which highly antimicrobial-resistant strains are a serious public health threat (Costa-Lourenço et al 2017). As some imipridone analogs can cross the bloodbrain barrier (Allen et al 2013(Allen et al , 2016, imipridone-based antimicrobials might hold promise in the treatment of bacterial meningitis, such as caused by N. meningitidis (Zouheir et al 2019).…”

Section: Imipridones As a New Antibiotic Scaffoldmentioning

confidence: 99%

Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development

et al. 2020

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Systematic genetic interaction profiles can reveal the mechanisms-of-action of bioactive compounds. The imipridone ONC201, which is currently in cancer clinical trials, has been ascribed a variety of different targets. To investigate the genetic dependencies of imipridone action, we screened a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout library in the presence of either ONC201 or its more potent analog ONC212. Loss of the mitochondrial matrix protease CLPP or the mitochondrial intermediate peptidase MIPEP conferred strong resistance to both compounds. Biochemical and surrogate genetic assays showed that impridones directly activate CLPP and that MIPEP is necessary for proteolytic maturation of CLPP into a catalytically competent form. Quantitative proteomic analysis of cells treated with ONC212 revealed degradation of many mitochondrial as well as nonmitochondrial proteins. Prompted by the conservation of ClpP from bacteria to humans, we found that the imipridones also activate ClpP from Escherichia coli, Bacillus subtilis, and Staphylococcus aureus in biochemical and genetic assays. ONC212 and acyldepsipeptide-4 (ADEP4), a known activator of bacterial ClpP, caused similar proteome-wide degradation profiles in S. aureus. ONC212 suppressed the proliferation of a number of Gram-positive (S. aureus, B. subtilis, and Enterococcus faecium) and Gram-negative species (E. coli and Neisseria gonorrhoeae). Moreover, ONC212 enhanced the ability of rifampin to eradicate antibiotic-tolerant S. aureus persister cells. These results reveal the genetic dependencies of imipridone action in human cells and identify the imipridone scaffold as a new entry point for antibiotic development.

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Section: Imipridones As a New Antibiotic Scaffoldmentioning

confidence: 99%

Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development

et al. 2020

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“…However, gonorrhea can develop into several inflammatory diseases including urethritis, endometritis, salpingitis, epididymitis, and pelvic inflammatory disease (PID). PID can lead to infertility and still births, whereas urethritis in males results in painful micturition and pain or tenderness in the testicles [3,4]. Previously, antibiotics such as penicillin have been highly effective in treating gonorrhea.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis

Yang

Dhital

Naderer

2019

JCM

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Gonorrhea is the second most frequently reported sexually transmitted infectious disease of bacterial origin in the world. Current empiric therapies rely on broad-spectrum antibiotics. However, treatment options are becoming limited due to the rise of drug-resistant gonorrhea. To control the rise of drug-resistant gonorrhea and to identify alternative treatment options, clinicians will have to increasingly rely on experimental evidence for the treatment of gonorrhea patients. Thus, we performed a systematic review and network meta-analysis of all randomized clinical trials about the efficacy and safety of various antibiotic regimens in adults with gonorrhea. We searched all references in Embase and PubMed from the date of their inception to January 2019, and then an updated search was performed in March 2019. Of the 28,843 identified references, 44 fulfilled our selection criteria. We used a network meta-analysis based on a frequentist approach to evaluate the efficacy and safety of 12 injectable and 11 oral antibiotics. The efficacy of treatments was ranked by p score and inconsistency was assessed by a back-calculation method. Certainty of evidence was evaluated by the GRADE system. For injectable drugs, there was no difference in efficacy between a reference antibiotic and other drugs. However, ceftriaxone had significantly better efficacy than cefuroxime (OR, 12.03; cephaloridine (OR, 42.41; kanamycin (OR, 5.45; penicillin (OR, 13.11;, and spectinomycin (OR, 4.70; 95% CI 1.62-13.62). Thus, ceftriaxone was the most effective injectable drug (p score of 0.924). As for oral drugs, azithromycin was the most effective compound (p score of 0.8633). There were no significant differences in safety between injectable and oral treatments. In our systematic review of randomized controlled trials, we found azithromycin and ceftriaxone to be the most effective antibiotics for the treatment of gonorrhea. This is in line with current guidelines which recommend a combination therapy of azithromycin and ceftriaxone for the treatment of gonorrhea due to increased antimicrobial resistance. Our analysis identified gentamicin and ofloxacin as alternative therapeutics to treat drug-resistant gonorrhea.

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“…In consequence, one can wonder to what extent the effect on preventive intentions yielded by this linguistic manipulation may lead to effective and lasting behavior, especially for individuals high in need for closure. In a current epidemiological context characterized by the advent of sexually transmitted infections and antimicrobial resistance considered as an "emerging global threat" (Cazanave, Manhart, & Bébéar, 2012;Unemo & Jensen, 2017;Ramalho da Costa-Lourenço;Barros dos Santos, Meurer Moreira, Longo Fracalanzza, & Bonelli, 2017), this last question is of a critical importance.…”

Section: Practical Implications Of the Studymentioning

confidence: 99%

A Strong Argumentative Orientation Makes the Cognitive Closure Easier: The Case for a Persuasive Health Message

Coppola¹,

Girandola²,

Camus³

2020

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The rationale of this study is that scalar adverbs are likely to act as a convenient means to achieve cognitive closure because they stress the argumentative orientation of the message. Based on this assumption, an experiment shows that the introduction of scalar adverbs in the message decreases the extent of its cognitive elaboration and increases its perceived quality and effectiveness for people high in need for closure, but not for people low in need for closure, for whom the outcomes are reversed with regard to perceived quality and persuasiveness of the message. To what extent such outcomes are likely to be affected by some variables traditionally studied in the persuasion literature is addressed in the discussion.

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Antimicrobial resistance in Neisseria gonorrhoeae : history, molecular mechanisms and epidemiological aspects of an emerging global threat

Cited by 80 publications

References 101 publications

Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development

Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development

Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis

A Strong Argumentative Orientation Makes the Cognitive Closure Easier: The Case for a Persuasive Health Message

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