INTRODUCTION:
Do you find it difficult to understand research papers due
to the heavy and novel biological terms? Don’t worry, I'm here to help you
understand research papers in a simplified way.
Have you ever wondered how antibiotic that doctors
prescribes work against bacteria and why bacteria are becoming resistant? What
are the ways to tackle this problem? In this post, I’ll explain this research
paper in the simplest possible way.
BODY:
What is an antibiotic?
Antibiotics a medicine that kills only bacteria and stops
them from growing. It works against only bacteria because they can grow,
reproduce, and live on their own. Antibiotics target specific parts of
bacterial cells, such as their cell walls or the proteins they produce. They
are like a bad guy who is hiding, and antibiotics are like the police who
arrest them and kill them.
Viruses are tiny particles, not cells. Viruses can't live or
reproduce by themselves. They must invade your body’s cells and use them like
factories to make more viruses. Antibiotics can’t get inside your cells to stop
viruses, and they don’t affect how viruses work. They are like hackers who get
into your computer. You need a completely different tool (antiviral medicine)
to stop them. Bacteria and viruses have completely different structures that
need different tools to kill them, based on which tool they can be killed.
How do antibiotics enter bacteria to act?
They enter through pores present on the cell membrane.
Porins are small protein channels that are like doors that let useful things
into the bacterial cell. They let small molecules like nutrients, water, or
certain antibiotics pass into the bacterial cell.
PORIN
AND ANTIBIOTIC INTERACTION
Why are bacteria becoming antibiotic-resistant?
Researchers at Kerala’s Rajiv Gandhi Centre for
Biotechnology have discovered that targeting the outer membrane of proteins
called porins in pathogenic bacteria can specifically fight against their
resistance to antibiotics.
Porins are found in the outer membrane of Gram-negative
bacteria such as Escherichia coli, Klebsiella pneumoniae, Neisseria
gonorrhoeae (which causes Gonorrhea, which is a common sexually
transmitted disease), etc., because the outer membrane is only found in Gram’s
Gram-negative bacteria, not in Gram-positive bacteria.
Gram-negative bacteria are those bacteria that have a thin
peptidoglycan layer (which makes the cell wall), but in addition to this, they
have a lipopolysaccharide layer or outer membrane, which prevents entry of
harmful substances, including some antibiotics and detergents. Whereas Gram’s
positive bacteria have a thick peptidoglycan layer.
Antibiotic resistance means bacteria change in a way that makes antibiotics stop working against them. Bacteria multiply fast and mutate (change their genes). Some mutations protect them from antibiotics.
Why use an antibiotic when prescribed?
When you take antibiotics when not needed or in the wrong
dose, bacteria get used to them. They mutate and survive, becoming stronger and
resistant. These new bacteria can't be killed by normal antibiotics anymore.
Resistance to antibiotics has become one of the most serious global health problems. Antibiotics enter bacterial cells through porins, so bacteria have evolved in such a way as to block antibiotics by reducing in number of porins and decreasing the flow or rush of antibiotics into bacteria. Bacteria make fewer porins, so fewer antibiotics can enter. This makes the bacteria less sensitive to drugs. Some bacteria change the shape or size of porins. The new structure blocks certain antibiotics from fitting through.
Researchers have identified a dynamic porin called CymAKp,
which is a specialized porin found in the outer membrane of the bacterium Klebsiella
pneumoniae. CymAKp is specially adapted to allow cyclic sugar (cyclic
or ring-structured sugar) into the cell.
How to overcome this problem?
It was found that certain antibiotics called aminoglycosides resemble
cyclic sugars and can travel through CymAKp to enter the bacteria.
Aminoglycosides are target the bacterial ribosome, which is the part of the
cell that makes proteins as they bind to the 30S subunit(smaller unit) of the
ribosome of bacteria, this stops protein production or causes bacteria to make
wrong proteins and as a result, the bacteria can’t grow or survive, and
eventually die. Some aminoglycosides are Streptomycin (an older drug used in TB
and some rare infections), Tobramycin (often used in lung infections, cystic
fibrosis), Amikacin (effective against some resistant bacteria), etc.
AMINOGLYCISIDES
Scientists worldwide are pioneering innovative strategies to
combat antibiotic-resistant bacteria. Some are:-
1. AI-Driven Discovery: Halicin
Researchers at MIT utilized artificial intelligence to
identify Halicin, a novel antibiotic effective against
various drug-resistant bacteria, including Clostridioides difficile and Acinetobacter
baumannii. Halicin operates by disrupting the bacteria's ability to
maintain an electrochemical gradient across their cell membranes, a mechanism
distinct from traditional antibiotics, making it harder for bacteria to develop
resistance.
2. Reviving Ancient DNA: Mammuthusin
At the University of Pennsylvania, scientists led by César
de la Fuente discovered Mammuthusin, an antibiotic compound
derived from the DNA of woolly mammoths. This peptide has shown effectiveness
against bacteria resistant to modern antibiotics, highlighting the potential of
ancient DNA in developing new antimicrobial agents.
3. New Antibiotic Class: Zosurabalpin
Swiss pharmaceutical company Roche, in collaboration with
Harvard University, developed Zosurabalpin, the first new
class of antibiotic in over 50 years targeting Gram-negative bacteria
like Acinetobacter baumannii. This antibiotic disrupts the
bacterial outer membrane, a novel mechanism that has shown promise in early
trials.
New
York Post+2The Times+2Financial Times+2Financial
Times
4. Soil-Derived Antibiotics: Teixobactin and Malacidin
Scientists have turned to soil microbes to discover new
antibiotics: WSJ
- Teixobactin:
Identified from previously unculturable bacteria, it has shown
effectiveness against Gram-positive pathogens without detectable
resistance. Wikipedia
- Malacidin:
Discovered through metagenomic analysis of soil samples, this compound
exhibits activity against multidrug-resistant bacteria.
5. Targeting Bacterial Proteins: DsbA Inhibitors
Researchers at Imperial College London found
that inhibiting the bacterial protein DsbA, which assists in
folding resistance proteins, can restore the effectiveness of existing
antibiotics against resistant strains. This approach offers a potential method
to combat resistance without developing new antibiotics.
6. Bacteriophage Therapy
Bacteriophages, viruses that infect bacteria, are
being explored as treatments for antibiotic-resistant infections. Researchers
are investigating engineered phages and phage-derived enzymes to target and
destroy resistant bacteria, offering a complementary approach to traditional
antibiotics.
7. Combination Therapies: FTS
FleurirABX, a pharmaceutical startup, developed FTS,
a combination of two existing antibiotics—fosfomycin and
trimethoprim-sulfamethoxazole. This synergistic combination has shown enhanced
effectiveness against resistant bacteria, potentially reducing the likelihood
of resistance development.
8. Photodynamic Therapy
Antimicrobial photodynamic therapy (aPDT) uses
light-activated compounds to produce reactive oxygen species that kill
bacteria. This method has demonstrated effectiveness against various
drug-resistant pathogens and is less likely to induce resistance due to its
multi-targeted approach.
CONCLUSION:
By understanding these interactions, research work revealed
a new route to overcome resistance. By studying every detail of pathways found
that a protein channel has a big impact on resistance to bacteria, as well as
an advantage for us to overcome the bacterial resistance.
Rajiv Gandhi Centre for Biotechnology’s director Chandrabhas
Narayan said bacterial resistance to antibiotics has become a major challenge
for the global medical community, which we should make the way for developing
next generation therapeutics designed to gain an advantage and using them in a
clever way against resistant pathogens.
Think for yourself what you can do to contribute to the
world to overcome this global threat?
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