Body as a Battlefield, Needed Potent Antibiotics

SREEKUMAR RAGHAVAN
We are just eight more years away
from celebrating the centenary of the discovery of Penicillin by Alexander
Fleming, the first antibiotic to be effective against serious diseases such as
meningitis, pneumonia septicaemia, tuberculosis, syphilis and staphylococcus
infections. It has saved millions of lives till date. Basically, the antibiotics conquer the
bacteria by interfering with the formation of its cell wall while it is growing.
It initially weakens and kills the bacteria.
When a harmful bacterium enters
our body, our body becomes a battlefield. And if our antibodies are unable to
resist them the antibiotic army is called in. However, as in any army
operations, there should be least harm caused to civilians and in this case our
cells themselves.
Drug Resistance
Antibiotics has become a potent
weapon in the hands of modern medicine practitioners to kill bacteria but some
new varieties of bacteria have developed resistance to almost all antibiotics
in the physician's arsenal. This is quite worrying. That apart there is also
the allegation that most antibiotics are overused causing harm to our
metabolism.
According to Dr Amy Cain of
Macquarie University, antimicrobial-resistant organisms kill 700,000 people a
year. The Covid-19 related hospitalisations could greatly increase that number
as hospitals are hot spots for drug-resistant bacteria.
Dr Cain says Gram-negative bacteria is present almost anywhere and the nasty ones such as E-Coli Pseudomonas Aeruginosa can cause a variety of infections and has become drug resistant. The Gram-negative bacteria has an outer membrane that gives them protection from antibiotics, detergents and antimicrobial enzymes. The class of anti-biotics called polymyxins directly attacks the bacterial cell walls but the weapon is required in doses that are toxic. Even at minimum dose levels it may harm the kidneys.
But Dr Cain believes that they have a solution now in the form of peptides (short strings of amino acids that form the building blocks of proteins). Such peptides with antimicrobial properties can be found in a variety of life forms and can kill microbes directly without impacting the host defence systems. Anti-microbial peptides can strengthen the patient's immune system and can be easily produced on industrial scale. In the lab, they derived it from marine lugworms and was found to be effective against multi-drug resistant gram-negative bacteria. But it turned out to be toxic to cells and destroyed red blood cells (RBC). They tweaked the peptides removing some components or mutating it but keeping the backbone intact. A functional genomic technique called ‘transpon directed insertion sequencing’ was used to prolong the antibiotic action. The results published in the journal Nature Communications was seen to be effective in mouse models but still a long way to go before it gets to human trials.
Haven't Understood the Enemy Yet
Researchers at McGill University
believe that all these years we haven't yet understood the enemy and its
structure properly even as we used the most potent weapons. Our individual cells contain specialised
compartments such as energy-producing mitochondria known as organelles but bacterial
cells were believed to be lacking those as they don’t
have membrane-bound organelles. But Stephanie Weber of McGill's Department of
Biology has now shown that bacteria indeed have specialised compartments. The
organelles are held together by 'sticky' proteins rather than a membrane. Since
the bacterial cells were small, Weber's team used an imaging technique-photo
activated localisation microscopy-to track the organelle-forming proteins. The
discovery by McGill's team may lead to development of a new generation of
antibiotics that are urgently needed to combat drug resistance.
Anti-Vitamins
The researchers at the University
of Gottingen and the Max Planck Institute for Biophysical Chemistry Gottingen
believe that new classes of anti-biotics can be produced from 'anti-vitamins'.
The results of the study were published in the journal Nature Chemical Biology.
Anti-vitamins are substances that inhibit the biological functioning of a
genuine vitamin. The study was conducted on a naturally occurring antivitamin of
vitamin B1. Some bacteria are able to produce a toxic form of this vital
vitamin B1 to kill competing bacteria. The antivitamin has only a single atom
in addition to the natural vitamin in a seemingly unimportant place. The one
extra atom in the antivitamins inhibited the functioning of the vitamin. The
researchers found that human proteins are able to cope relatively well with the
antivitamins and continue with its normal life. This is because human proteins do
not bind to the anti-vitamin at all or in such a way that they are 'poisoned'.
It was found that antivitamins had adverse impact on bacteria but not on human
proteins. This can pave the way of development of 'antivitamin' antibiotics.
The Future
Research has shown the potentially inappropriate use of antibiotics with
the intention of preventing the development of bacterial infections. This can
also cause drug resistance and also build up toxicity in the body, according to
University of North Carolina. We aren’t fully equipped with the right weapons in
the war against bacteria especially the drug resistant ones. But new insights
on the structure of the bacterial cells itself gives hope of development of more
potent antibiotics. After all a war is won only when one understands the strength
and weaknesses of the enemy.
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