Transcript Analysis of mutations within multiple genes associated

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
Introduction to antimicrobial resistance
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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 1980’s
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)
(Prof. Robinson, 2004)
Paper Specific
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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
Methods
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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.
methods continued…
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Polymerase Chain Reaction (PCR) amplification
and DNA sequencing were performed to the loci
penA, ponA, mtrR, penB and gyrA and parC using
various primers.
Results
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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
results continued…
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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.
World Application
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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)
Works Cited
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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/medicalgenetics/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