Analysis of mutations within multiple genes associated with resistance in clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistance phenotype - PowerPoint PPT Presentation

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Analysis of mutations within multiple genes associated with resistance in clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistance phenotype

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Title: Analysis of mutations within multiple genes associated with resistance in clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistance phenotype


1
Analysis of mutations within multiple genes
associated with resistance in clinical isolate of
Neisseria gonorrhoeae with reduced ceftriaxone
susceptibility that shows a multidrug-resistance
phenotype
  • Masatoshi Tanaka, Hiroshi Nakayama, Kozaburo
    Huruya, Ichiro Konomi, Shinichiro Irie, Akiko
    Kanayama, Takeshi Saika, Intetsu Kobayashi

2
Introduction to antimicrobial resistance
  • Since the development of Penicillin in 1920, some
    disease producing bacteria have been developing
    resistance to many antibiotics and other
    treatments
  • This problem has greatly increased in profundity
    beginning in the late 1980s
  • Evolutionarily, there are at least three main
    ways that bacteria become less susceptible or
    resistant to drug treatment mutation,
    conjugation, and transposition (Thompson, Bert.
    1994)

3
(Prof. Robinson, 2004)
4
Paper Specific
  • Recently found a strain of N. gonorrhoeae that is
    resistant to ceftriaxone treatment.
  • This strain is also resistant to multiple other
    drug treatments.
  • Research has shown that resistance of other drug
    treatments are likely due to mutations at penA,
    mtrR, and penB loci.
  • This study was aimed at discovery of molecular
    basis for resistance of ceftriaxone

5
Methods
  • 398 clinical isolates were collected for the
    study and screened for antimicrobial
    susceptibility.
  • The testing included susceptibility analysis of
    penicillin G, tetracycline, ceftriaxone,
    cefixime, ciprofloxicin, azithromycin and
    spectinomycin.
  • Guidelines set by the National Committee for
    Clinical Laboratory Standards (NCCLS) were
    followed
  • After the testing five isolates were further
    identified as GP853, GP984, GP986, GP998 and
    A69W.

6
methods continued
  • Polymerase Chain Reaction (PCR) amplification and
    DNA sequencing were performed to the loci penA,
    ponA, mtrR, penB and gyrA and parC using various
    primers.

7
Results
  • The strain GP853 was found to have reduced
    susceptibility to ceftriaxone, as well as
    penicillin, tetracycline, azithromycin and
    ciprofloxacin.
  • At the penA gene, mutations were found that coded
    for resistance to penicillin.
  • Mutations at the mtrR gene were found to be where
    reduced susceptibility to ceftriaxone was coded
    for.
  • Looking at the penB gene, mutations coding for
    reduced permeability of penicillins and
    tetracyclines were found

8
results continued
  • At the gyrA and parC genes, mutations and amino
    acid substitutions were found that resist
    ciprofloxacin.
  • In the domain of penA, the horizontal gene
    transfer of antimicrobial resistant material from
    other Neisseria species is suggested to be the
    form of evolution causing resistance to
    cephalosporins in the GP853 strain.

9
World Application
  • Increased public knowledge on the proper use of
    antibiotics and treatments.
  • Reduced use of antibacterials
  • More research on a molecular level of the
    logistics about resistance and ways to beat it.
    (Antimicrobial resistance, 1997)
  • Surveillance by hospitals, researchers and
    private doctors should be conducted on which
    drugs are resistant to antimicrobials.
    (Antimicrobial resistance, 1997)

10
Works Cited
  • Tanaka M, Nakayama H, Huruya K, Konomi I, et al.
    Analysis of mutations within multiple genes
    associated with resistance in a clinical isolate
    of Neisseria gonorrhoeae with reduced ceftriaxone
    susceptibility that shows a multidrug-resistant
    phenotype. Antimicrobial Agents 2006, 20-26
  • Prof. Robinson. History of antibiotic
    resistance. Antibacterial resistance and
    Mycobacterium tuberculosis. Dec. 10, 2006. UCLA.
    Winter, 2004. http//ftaylor.bol.ucla.edu/history.
    html
  • Gray-Owen, Scott D. Host cellular response to
    the pathogenic Neisseria. Dec. 10, 2006. The
    University of Toronto. http//www.utoronto.ca/medi
    calgenetics/Pls/Gray-Owen.htm
  • Antimicrobial resistance. National Foundation
    for Infectious Diseases. Dec. 11, 2006. April
    1997. http//www.nfid.org/factsheets/antimicrobial
    .html
  • Thompson, Bert. Bacterial Antibiotic resistance
    and Evolution. Dec. 9, 2006. Reason and
    Revelation, 1994 14(8) 61-63
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