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allied
academies
September 20-21, 2017 | Philadelphia, USA
Global summit on
TUBERCULOSIS AND LUNG DISEASE
Int J Respir Med 2017 Volume 2 Issue 2
S
tatement of the Problem: Mycobacteria, especially
M. tuberculosis
is one of the most dangerous types of
microorganisms to cause diseases and mortality. While
specific resistance of
M. tuberculosis
to drug therapy is
thought to be caused by antibiotics action, the general
resistance is due to the known distinctive structure of
mycobacterial cell wall (CW). Owing to the CW structure,
mycobacteria are protected from the penetration of
overwhelming number of soluble substances including
majority of antibiotics and common chemical disinfectants
and biocides. Methodology & Theoretical Orientation: In the
presentedwork, protonated polydiallylamines (PDAAs) based
on trifluoroacetic salts of the secondary and tertiary (with
Me/Et N-substituents) diallylamines have been synthesized
that may be defined as the representatives of a novel
family of synthetic water-soluble cationic polyelectrolytes.
The in vitro antimicrobial activity of PDAAs against
M.
tuberculosis
and
M. smegmatis
including “nonculturable”
dormant
M. tuberculosis
cells has been evaluated, as well
of quaternary counterpart poly(diallyldimethylammonium
chloride) (q-PDADMAC) and current antibiotics rifampicin
and ciprofloxacin as control systems to compare activities
at the similar conditions. Examination of
M. smegmatis
cells in presence of PDAAs/(rifampicin, isoniazid) under
an optical microscope in the epifluorescence modes has
been performed. Studies on electrophoretic mobility of
M.
smegmatis
cells and some model liposomes have revealed a
small negative charge of the cells outer surface and recharge
in the presence of cationic PDAAs. Conclusion & Significance:
The PDAAs possess high mycobactericidal activity including
dormant
M. tuberculosis
cells at a variable time treatment
(1.5-72 h) and cells concentration (105-107 CFUmL-1), unlike
q-PDADMAC and the antibiotics which are significantly less
efficient or inactive at all (at a maximal tested concentration
of 500 g mL-1). To all appearances, PDAAs’ impact does not
target specific metabolic processes, unlike antibiotics, and is
related to disturbance of the integrity of mycobacterial outer
bilayer followed by fatal damage of the inner membrane
permeability of mycobacterial cells.
Speaker Biography
Larisa Timofeeva is an expert in the field of processes for preparing novel cationic
polymers, including mechanism and kinetics of polymerization reactions in solutions
and theory of monomers reactivity, as well as novel polyamines with antimicrobial
activity. She has years of experience in scientific research work in Topchiev Institute
of Petrochemical Synthesis of RAS. Last 15 years, her research activity was aimed
at solving the known problem of polymerization of diallylammonium monomers.
She has developed an approach which allowed to obtain protonated polyamines
of poly(diallylammonium) series with relatively high molecular weight. It has
been discovered that polymers of this novel family exert strong biocidal action on
multiple clinically relevant pathogens including rare activity against mycobacteria
M.
tuberculosis
.
e:
timofeeva@ips.ac.ruNonquaternary diallylammonium polymers with different amine structure and their biocidal effect on
M. tuberculosis and M. smegmatis
Larisa M. Timofeeva
RC Biotechnology TIPS RAS, Russia