Emergence and spread of resistant N. meningitidis implicated in invasive meningococcal diseases during the past decade (2008–2017)

Zouheir, Yassine; Atany, Taha; Boudebouch, Najma

doi:10.1038/s41429-018-0125-0

Cited by 17 publications

(17 citation statements)

References 16 publications

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“…In addition, this particular clonal complex in MenB and MenC cases is non-susceptible to ciprofloxacin, leading to warnings that this antibiotic should be prescribed with caution as a prophylactic treatment. [21][22][23] Prevention and control strategies There are a range of prevention and control strategies employed across the Asia-Pacific region; however, most countries do not include meningococcal vaccination as part of their National Immunization Programs (NIPs). Although practices vary, chemoprophylaxis is commonly prescribed, with immunization only being recommended for those in high-risk groups.…”

Section: Serogroup Distributionmentioning

confidence: 99%

Meningococcal disease surveillance in the Asia–Pacific region (2020): The global meningococcal initiative

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et al. 2020

Journal of Infection

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The incidence of IMD is low and similar across the represented countries (< 0.2 cases per 10 0,0 0 0 persons per year), with the predominant serogroups of Neisseria meningitidis being B, W and Y, although serogroups A and X are present in some areas. Resistance to ciprofloxacin is also of concern, with the close monitoring of antibiotic-resistant clonal complexes (e.g., cc4821) being a priority. Meningococcal vaccination is only included in a few National Immunization Programs, but is recommended for high-risk groups, including travellers (such as pilgrims) and people with complement deficiencies or human immunodeficiency virus (HIV). Both polysaccharide and conjugate vaccines form part of recommendations. However, cost and misconceptions remain limiting factors in vaccine uptake, despite conjugate vaccines preventing the acquisition of carriage.

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Section: Serogroup Distributionmentioning

confidence: 99%

Meningococcal disease surveillance in the Asia–Pacific region (2020): The global meningococcal initiative

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Bai

Borrow

et al. 2020

Journal of Infection

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“…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). Further refinement of the imipridone scaffold may improve its activity against Gram-negative species.…”

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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“…Globally, resistance to antibiotics in N . meningitidis isolates is relatively rare, but the emergence of meningococcal strains with decreasing susceptibility to antibiotics is of increasing public health concern [ 45 ]. Alterations in the gene encoding PBP2 ( pen A) are associated with reduced affinity to penicillin and thus a decrease in susceptibility to the antibiotic [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of Neisseria meningitidis isolates recovered from patients with invasive meningococcal disease in Colombia from 2013 to 2016

et al. 2020

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Background Neisseria meningitidis is a significant cause of morbidity and mortality worldwide. Meningococcal isolates have a highly dynamic population structure and can be phenotypically and genetically differentiated into serogroups and clonal complexes. The aim of this study was to describe the phenotypic and genotypic characteristics of invasive isolates recovered in Colombia from 2013 to 2016. Methodology A total of 193 invasive isolates were analyzed. Phenotypic and genotypic characteristics were determined by serotyping, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. Results Based on the results, meningococcal serogroups C, B and Y were responsible for 47.9%, 41.7%, and 9.4% of cases, respectively, and the distribution of serogroups B and C changed over time. Fifteen clonal groups and 14 clonal complexes (cc) were identified by PFGE and genome sequencing. The main clonal group included serogroup B isolates with sequence type (ST)-9493 and its four single-locus variants, which has only been identified in Colombian isolates. The clonal population structure demonstrates that the isolates in this study mainly belong to four clonal complexes: ST-11 cc, ST-32 cc, ST-35 cc and ST-41/44 cc. Thirty-eight pen A alleles were identified, but no correlation between MICs and specific sequences was observed. Conclusion This study shows that most meningococcal isolates recovered from patients with invasive meningococcal disease in Colombia are strains associated with distinct globally disseminated hyperinvasive clones.

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Emergence and spread of resistant N. meningitidis implicated in invasive meningococcal diseases during the past decade (2008–2017)

Cited by 17 publications

References 16 publications

Meningococcal disease surveillance in the Asia–Pacific region (2020): The global meningococcal initiative

Meningococcal disease surveillance in the Asia–Pacific region (2020): The global meningococcal initiative

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

Molecular characterization of Neisseria meningitidis isolates recovered from patients with invasive meningococcal disease in Colombia from 2013 to 2016

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