Understanding AMR & New ways to tackle it

Sourav Chakraborty4th year, G.C.T.S

Ashram More, Asansol

CONTENTS

• UNDERSTANDING AMR ……………………..……………………………….• ITS GLOBAL EFFECT …………………………………………………………• ITS REASON TO PREVIAL IN 21ST CENTURY …………………………….• HOW IT COULD TO STOPPED ……………………………………………….• TARGETS FOR RESISTANT FREE ANTIBIOTICS ………………………..

– ANTIBIOTICS NETWORK BIOLOGY ……………………………………………………– SPECIFY ANTIBIOTICS MEDIATED CELL DEATH ……………………………….......– BACTERIOPHAGE TECHNIQUE ………………………………………………………..

• BACTERIOPHAGE TECHNIQUE ……………………………………………• CONCLUSION …………………………………………………………………..

UNDERSTANDING AMR

Antimicrobial resistance (AMR) is when a microbe evolves to become more or fully resistant to antimicrobials which previously could treat it. Resistance can appear spontaneously due to random mutations; or more commonly following gradual buildup over time, and because of misuse of antibiotics or antimicrobials. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR); or sometimes superbugs. Antimicrobial resistance is on the rise with millions of deaths every year. A few infections are now completely untreatable due to resistance. All classes of microbes develop resistance (fungi, antifungal resistance; viruses, antiviral resistance; protozoa, antiprotozoal resistance; bacteria, antibiotic resistance).

Drug inactivation or modification: for example, enzymatic deactivation of penicillin G in some penicillin-resistant bacteria through the production of β-lactamases.

Alteration of target site.

Inhibition of the drug target.

Reduced drug accumulation: by decreasing drug permeability or increasing active efflux

The Global Effect of AMRo Ineffective treatment to microbial attack due to over exposure to antibiotics.

o Less potency to microbes( delayed action).

o Hence more potent antibiotics are required causing huge side effects.

o In severe patients if resistance is seen, even death maybe at stake. http://save-antibiotics.blogspot.in/

Why AMR is prevailing in the 21st century?

Doctors prescribing antibiotics even without any serious infection.

Ineffective diagnosis leading to prescribing broad spectrum antibiotics always.

Less awareness on the dose and intake of antibiotics.

Not completing antibiotic courses.

Over exposure to bacterial environment due to improper sanitation in villages.

High cost of selective antibiotics due to which common man preferring cheaper same antibiotics in most infections.

Normal prevention of AMRPATIENT:

• Only take antibiotics when necessary•Don’t save antibiotics for the next course•Complete the whole course•Don’t take antibiotics without prescription•Don’t ask antibiotics to even be prescribed•Maintain proper hygiene

FOR HEALTH CARE PROFESSIONAL:

• Not to prescribe antibiotics for viral infection•Trying to prescribe only the best antibiotic for the purpose•To know the trend of resistance in the region.

TARGETS FOR DEVELOPING RESISTANCE FREE ANTIBIOTICS

In the search for resistant free antibiotics development, researchers are always searching for newer specific targets which are less susceptible for mutation and resistant development. The targets are identified for each species according to their life cycle and mode of replication and the most suitable targets are chosen which can easily be either manipulated or inhibited. The targets that will be discussed are unique in nature because of the techniques applied and still are under research, still recent progress shows that they can really be efficient in tackling resistant.

TARGETS FOR DISCUSSION:

• Antibiotic network biology.

•Bacteriophage technique.

Antibiotic network biology

Bioinformatics approach that utilizes screening of the genetic information for understanding the bacterial cell and its mechanism for drug resistance of other ways to kill the

bacteria

Helps for the selection and development of novel antibiotics for selective action and for higher therapeutic action, due to

genetic information pertaining to resistance, it can be tackled

For example, recent screens for antibiotic susceptibility in a single-gene deletion library of non-essential genes in E. coli  and a transposon mutagenesis library in Pseudomonas aeruginosa have provided important insights into the numbers and types of genes that affect treatment efficiency.

BACTERIA – EXPOSED TO DIFFERENT ANTIBIOTICS.

EXPOSED FOR A PERIOD OF TIME SO THAT RESISTANCE DEVELOPS TO MOST ANTTIBIOTICS.

Information pertaining to mutation mechanism obtained for allThe test gives a better understanding for which antibiotic would grow

resistance the least with time If no resistance occurs by any chance then a novel approach could be

developed with such a drug

GENE EXPRESSION DATA THROUGH HIGH GENETIC SCREENS .

IDENTIFICATION OF BIOCHEMICAL PATHWAYS DONE BY THE BACTERIA.

IDENTIFICATION OF ITS MUTAGENIC PROPERTY.

METHODOLGY:

NOTES FOR THE EXPIREMENT:• Choosing the time to be exposed to antibiotic is essential-

• For isolated microbes 11-14days• For patients 5-9days• For serious patients 1-2days

http://www.atsjournals.org/doi/abs/10.1164/rccm.200908-1210oc

Bacteriophage technique

Bacteriophages (Greek for ‘eaters of bacteria’) are the most abundant life forms on Earth, with an estimated ten thousand billion billion billion (1031) bacteriophages inhabiting water, plants, sewage and the digestive tract of species ranging from mosquitos to fish to humans. A bacteriophage rapidly kills its bacterial host, replicating itself in the process, thereby creating an escalating swarm that continues to destroy until the host is eliminated.

THESE ARE VIRUSES ONLY WHICH ITSELF INFECT THE BACTERIA FOR HOST.

THEY THEN DESTROY THE BACTERIAL CELL BY GROWING AND REPLICATING.

THEY THEN ITSELF GETS DESTROYED AND HENCE ANTIBACTERIAL ACTION IS DONE.

BEST PART IS, IF RESISTANCE DEVELOPES THEN SINCE WE ARE APPLYING A VIRUS THEN THEY EVEN CAN RESIST THE RESISTANCE MECHANISM BY ALTERING THEMSELVES.

Our approach has several potential advantages compared to traditional antibiotic therapy:

•Potential for fewer side effects•Phage therapies are highly specific to their target bacterial species.  They cannot kill mammalian cells and have minimal impact on beneficial bacteria.

•Ability to treat multi-drug resistant bacteria•Phages attack bacteria through a unique mechanism, therefore, they are likely to bypass the bacterial defense processes aimed towards antibiotics, thereby providing an alternative therapeutic option for difficult-to-treat, multi-drug resistant infections.

•Unique potential for resistance management

•Ability to disrupt biofilms•Biofilms are almost impenetrable layers filled with aggregated bacteria and other extracellular components, which shield the bacteria. These complex communities of bacteria, present in the majority of infections, can render conventional antibiotics almost completely ineffective. By contrast, some bacteriophages are able to penetrate biofilms and replicate locally to high levels, producing a strong therapeutic effect.

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