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Microbiology: Current Research 2017
Volume 1 Issue 2
Microbes Infection 2017
Notes:
Page 31
September 28-29, 2017 | London, UK
Microbes Infection
38
th
Annual congress on
Mechanism that enhances the action of rifampicin
on multi-resistant mycobacteria tuberculosis when
it is administered in combination with an iodine-
containing anti-infection drug
Gulnara A Yuldasheva, Bakhytzhan F Kerimzhanova, Marina B Lankina,
Marat E Kulmanov
and
Aleksandr I Ilin
The Scientific Center for Anti-infective Drugs, Republic of Kazakhstan
A
new iodine-containing anti-infection drug (AID)
has been created possessing a broad spectrum of
antimicrobial and antiviral effects at the Scientific Center for
Anti-infectious Drugs (Republic Kazakhstan). Unlike other
iodine-containing drugs, AID is used for oral administration.
AID promotes an increase in the permeability of the cell
membrane and bacterial wall and has membraneolytic
capacity.
In vivo
and
in vitro
experiments AID was found
to possess an anti-tuberculosis effect. In clinical isolates of
mycobacteria isolated in clinical trials from patients suffering
from multidrug-resistant pulmonary tuberculosis,
in vitro
as well as
in vivo
sensitivity of
Mycobacterium tuberculosis
to rifampicin, isoniazid, streptomycin, ethambutol was
found restored and enhanced where AID acted together
with antibiotics. The active center of AID is a complex of
magnesium ion with lithium halide, molecular iodine and
triiodide. Therefore, it can form a complex with rifampicin
(Fig.1). When interacting with mycobacterium DNA, the
nucleotides displace the peptides and form a complex with
the molecular iodine and the lithium halide. In paper, the
crystal structure core of DNA-dependent RNA polymerase
(RNAP) complex with rifampicin was determined; it is
shown that rifampicin inhibits the β-loop of RNAP at a
distance of about 12.1 Å from the active center of RNAP.
Distinguished are amino acid residues of RNAP, which form
hydrogen bonds with rifampicin. In paper, it is shown that the
resistance to rifampicin is caused by mutations in the DNA
of
Mycobacterium tuberculosis
that lead to the replacement of
amino acid residues in the RNAP β-loop region that interacts
with rifampicin and, as a consequence, to the weakening
of binding energy of amino acid residues with rifampicin.
Using the molecular modeling method, we have shown that
an increase in the action of rifampicin and the restoration
of Mycobacterium tuberculosis’s sensitivity to it when
administered together with AID are due to the following two
reasons: (1) the AID active center binds both the bacterial
DNA and the active center of RNAP, (2) when amino acid
residues of RNAP are inhibited by the rifampicin complex
with the AID active center, the inhibitory energy is enhanced.
Biography
Gulnara A Yuldasheva received her Ph.D from Central Asian Department of
National Academy of Sciences. She is now a Leading Research in Scientific
Center for Anti-Infective Drug, Kazakhstan, Almaty. She is membership
American Chemical Society She works to use quantum-chemical methods.
She has an interest in a mechanism the inhibition of DNA HIV replication,
mechanisms of anti-cancer action of complex iodine with lithium halogenides
and bioorganic ligands and influence on mechanisms biochemical reaction.
of iodine complex compounds. Her current research is focused to find of new
compounds having anti-infection and anticancer activity.
yuldasheva57@rambler.ruGulnara A Yuldasheva et al., Microbiology: Current Research 2017