Article

Emergence in Italy of a Neisseria meningitidis Clone with Decreased Susceptibility to Penicillin

Department of Infectious, Parasitic & Immuno-mediated Diseases, Istituto Superiore di Sanita', Rome, Italy.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 09/2004; 48(8):3103-6. DOI: 10.1128/AAC.48.8.3103-3106.2004
Source: PubMed

ABSTRACT

A rise in invasive diseases due to Neisseria meningitidis C:2b:P1.5 with decreased penicillin susceptibility occurred in Italy during the last 2 years. Real-time PCR identified the
Peni phenotype, and the penA sequence revealed the mosaicism of the gene. Molecular analyses assigned the isolates to a single emergent clone of the hypervirulent
A4 cluster.

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Available from: Paola Stefanelli, Jan 07, 2014
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    • "Initially it produces general symptoms like fatigue; it can rapidly progress from fever, headache, neck stiffness, nausea, and partial lesions on skin, coma and death [4]. Neisseria meningitidis serotypes are also showing resistance towards the commonly prescribed antibiotics such as penicillin [5], ciprofloxacin [6], ceftriaxone [7], rifampin [8], and polymyxin . In particular, N. meningitidis serogroup B is known for exhibiting multi-drug resistance among other serotypes. "
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    ABSTRACT: Neisseria meningitidis (N. meningitidis) is a non-motile, Gram-negative bacterium. N. meningitidis is often referred as meningococci and causes cerebrospinal fever and bacterial meningitis. Although antibiotics such as penicillin, ciprofloxacin, ceftriaxone, rifampin and polymixin were used to treat bacterial meningitis, but N. meningitidis exhibits multi drug resistance. Therefore, designing novel inhibitors against N. meningitidis would be useful for developing therapies directed towards management of cerebrospinal fever and bacterial meningitis. Genome sequence of N. meningitidis was explored using sRNAPredict tool to identify 249 sRNA candidates of which 68 were enzymes and rests were non enzymes. The enzyme GTP pyrophosphokinase plays a pivotal role in the growth and metabolisms of the pathogen and non-homologous to Homo sapiens, so it was selected as a potential drug target against N. meningitidis. Homology model was built to GTP pyrophosphokinase using Modeller 9v13. Model with lowest DOPE score was selected and validated using PROCHECK, ProSA and ProQ. Published inhibitors such as alpha beta ethylene-ATP, microccin, tetracycline, thiostrepton and viomycin were selected for shape based similarity screening against ASINEX database to generate an in-house library. Docking studies were accomplished using Glide v6.2 for in-house library with GTP pyrophosphokinase which revealed 39 potential leads. Binding free energies (ΔG score) of resulted leads and existing inhibitors were compared to propose five compounds as potent inhibitor of GTP pyrophosphokinase. Lead1 showed lowest ΔG score of -63.65 kcal/mol with strong hydrogen bonding network and with good van der Waals interactions. Five best leads are observed to obey the pharmacological properties at par with 95% of the existing drug molecule. Thus, the lead1 can freezes the functional activity of GTP pyrophosphokinase in the purine metabolism necessary for the replication and DNA repair, to halt proliferation of the of N. meningitidis.
    Full-text · Article · Mar 2015 · International Journal of Scientific and Engineering Research
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    • "Initially it produces general symptoms like fatigue; it can rapidly progress from fever, headache, neck stiffness, nausea, and partial lesions on skin, coma and death [4]. Neisseria meningitidis serotypes are also showing resistance towards the commonly prescribed antibiotics such as penicillin [5], ciprofloxacin [6], ceftriaxone [7], rifampin [8], and polymyxin . In particular, N. meningitidis serogroup B is known for exhibiting multi-drug resistance among other serotypes. "

    Full-text · Article · Feb 2015 · International Journal of Scientific and Engineering Research
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    • "Beta lactams such as penicillin G are still the first line antibiotics in the treatment of invasive meningococcal infections. However, an increasing number of meningococcal isolates showed reduced susceptibility to penicillin G in several countries (Vázquez, 2001; Antignac et al., 2003b; Stefanelli et al., 2004). Alterations in the penA gene, encoding the penicillin binding protein 2 (PBP2), are directly linked to meningococcal reduced susceptibility to penicillin G (Spratt, 1994; Antignac et al., 2003a). "
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    ABSTRACT: Culture-confirmed diagnosis of meningococcal invasive infections is often hindered by early antibiotic treatment. Nonculture molecular standardized methods are now essential tools for the immediate management of meningococcal infections. The European Monitoring Group on Meningococci (EMGM) recommends the following measures. (1) The implementation of standardized protocols of extraction methods for DNA isolation from clinical specimens for PCR-based identification and genogrouping of Neisseria meningitidis. (2) The use of molecular approaches (sequencing of target genes) for the determination of meningococcal susceptibility to antibiotics, such as sequencing of penA and rpoB genes for susceptibility to penicillin G and rifampicin, respectively. (3) The use of nonculture strain characterization by multilocus sequence typing (MLST) and sequence typing of porA and fetA. These approaches can be implemented either by individual reference laboratories or through collaboration and referral between centres.
    Preview · Article · Feb 2007 · FEMS Microbiology Reviews
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