‘Keep the cell wall shut’ model to fight bacterial infection - Seeker's Thoughts

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‘Keep the cell wall shut’ model to fight bacterial infection

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The connection between life and bacteria remain sometimes positive and sometimes negative. Human body has multiple bacteria in our bodies, who resides in colonies in guts or skins.
The interesting fact about bacteria is that they have survived long.  

Our predecessors have been bacteria, and perhaps longest living beings on the earth. The total number of bacteria is astounding — five million trillion trillion (a five with 30 zeros after it). To be precise that will not be wrong to call that there are far more bacteria on Earth than there are stars on the universe.

Bacteria which resides in our guts effect human so much that they even manipulate that we like socialisation or not. In fact, the death of gut bacteria can lead to human in to depression.

They also help with immunity, making the body less hospitable to bad bacteria and other harmful pathogens

However, the problem is often when a bacteria spreads among humans and harms them.

What is a bacteria?

Bacteria are microscopic, single-cell organisms that live almost everywhere. Bacteria live in every climate and location on earth. Some are airborne while others live in water or soil. Bacteria live on and inside plants, animals, and people.

The word "bacteria" has a negative connotation, but bacteria actually perform many vital functions for organisms and in the environment. For example, plants need bacteria in the soil in order to grow.

The evolution of Bacteria.

The earliest bacteria seemed to be on the earth for the last 3.8 to 4 billion years.  Like any other living entity, they depend upon the environment.

Humans have evolved; however, the term evolution works on almost ‘every’ species. Bacteria also have evolved and adapted to their environment for their survival, and that is when their existence comes to an struggle with humans.

Some of the bacteria which are unsafe for human health, they feed on human’s health. This ends often in an human infection or a disease. Bacteria keep on feeding, until the cure is found. 

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What is bacterial infection?

A bacterial infection is a proliferation of a harmful strain of bacteria on or inside the body. Bacteria can infect any area of the body. Pneumonia, meningitis, and food poisoning are just a few illnesses that may be caused by harmful bacteria. 
Image Credit - One health 

Bacteria come in three basic shapes: rod-shaped (bacilli), spherical (cocci), or helical (spirilla). 
Bacteria may also be classified as gram-positive or gram-negative. Gram-positive bacteria have a thick cell wall while gram-negative bacteria do not. Gram staining, bacterial culture with antibiotic sensitivity determination, and other tests are used to identify bacterial strains and help determine the appropriate course of treatment.

What is the difference between Bacteria and virus?

Bacteria and viruses are different types of pathogens, organisms that can cause disease. Bacteria are larger than viruses and are capable of reproducing on their own. Viruses are much smaller than bacteria and cannot reproduce on their own. 
Picture Credit - One health

Instead, viruses reproduce by infecting a host and using the host's DNA repair and replication systems to make copies of itself.

Types of Infections caused by Bacteria

The symptoms of a bacterial or viral infection depend on the area of the body that is affected. Sometimes the symptoms of the two can be very similar. For example, runny nose, cough, headache, and fatigue can occur with the common cold (virus) and with a sinus infection (bacteria).
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A doctor may use the presence of other symptoms (such as fever or body aches), the length of the illness, and certain lab tests to determine if an illness is due to a virus, bacteria, or some other pathogen or disease process.

Bacterial skin infections are usually caused by gram-positive strains of Staphylococcus and Streptococcus or other organisms.

Bacterial infections are one cause of foodborne illness as well. Nausea, vomiting, diarrhea, fever, chills, and abdominal pain are common symptoms of food poisoning. Raw meat, fish, eggs, poultry, and unpasteurized dairy may harbor harmful bacteria that can cause illness. Unsanitary food preparation and handling can also encourage bacterial growth.

Many sexually transmitted diseases (STDs) are caused by harmful bacteria. Sometimes, these infections aren't associated with any symptoms but can still cause serious damage to the reproductive system.

Antibiotics are medications that fight bacterial infections. They work by disrupting the processes necessary for bacterial cell growth and proliferation.

The New Challenge in stopping the infection caused by bacteria.

Sometimes, bacteria develops anti-biotic resistance.

Even as we discover drugs and molecules to fight them, bacteria quickly mutate, resist. And we humans have tried various ways to fight these infections using herbs and drugs since ancient times. 

Methods to fight against bacteria

Dr Rustam Aminov writes in his paper: “A brief history of the antibiotic era: Lessons learned and challenges for the future” (Frontiers in Microbiology, 8 Dec 2010) that ancient Egyptians tried using poultices of moulded bread against infection and ancient Sudanese skeletons had traces of the antibiotic tetracycline — obviously from some herb they would have used against microbial infections.

The day of modern medical treatment is recent. Dr. Hara discovered the compound arsphenamine to fight syphilis in 1909 and Dr. Bertheim synthesised it and called it salvarsan in 1910. And in 1928, Alexander Fleming discovered penicillin, which could kill a large number of infecting bacteria.

What is the problem with bacteria?

Even as we discover more and more drugs and molecules to fight them, bacteria quickly change their genetic composition by mutation and resist the action of the drug.

The crucial is to understand the biological steps involved in bacterial infections. That is when the weakest zone can be identified which may ultimately lead to a victory against bacteria.

It is towards this challenge that microbiologists have been studying the molecular biology of bacteria using the species called Escherichia coli (E. coli for short) as the model organism in the laboratory. 
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We now know that bacterial cells are surrounded by a protective cell wall made up of a large sac-like structure called peptidoglycan or PG. The PG that bacteria use to build their cell walls is specific to them alone, and not found anywhere else on earth.

The PG is a baglike structure which is made of sheets of two sugar molecules, NAG and NAM, linked together as long chains.

These sheets are cross-linked or stapled together to form a continuous layer around the bacterial cells.

Therefore, as the bacterium grows in size, this PG bag also has to expand. That means the stapler has to be opened, new material incorporated and the bag stapled again into compactness for successful bacterial growth.

Key step

An important step towards this has been made by Dr. Manjula Reddy and her colleagues at the Centre for Cellular and Molecular Biology (CCMB) at Hyderabad.

Her group has been studying the basic biology behind how the bacterium builds its cell wall, how the bag opens for growth, and what molecules help in opening the bag.

Her group has identified a particular class of enzymes, which are responsible for unstapling the PG bag (see their publications: Singh et al., Mol. Microbiol., 2012; 86(5), 1036-1051; Singh et al., PNAS, 112, 10956-10961; Chodisetti et al., PNAS, April 2, 2019; https://doi.org/10.1073/pnas.1816893116).

They further showed that if any or all of these enzymes are removed from the bacterium (using genetic engineering methods), the PG bag does not open, starving the bug to death.

What does this mean? If we can find molecules or methods to inhibit these enzymes, and thus arrest the infecting bacterium from making its protecting cell wall, we will have found a way to overcome infection and offer safety. 
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A differing approach is used against the bacteria

Incidentally, the classical antibiotic, penicillin, inhibits the enzymes which help in re-stapling the once-opened cell wall, thus weakening the bug and killing it.

While this approach is a “do not close the wall” one, the CCMB approach is a “keep the cell wall shut and never open it”.  

The currently popular class of antibiotics, called the fluoroquinolones (such as ciprofloxacin), acts not on the cell wall, but inhibits the enzymes that allow the DNA of the bacterium to open up and replicate itself.

 These drugs thus inhibit the reproduction and repair of genes of the infecting bacteria.

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