A New Breakthrough in Bacterial Infection Control

    The battle against “war bugs'' or antibiotic resistant bacteria (ARB) has been claimed to be one of the biggest global health challenges of the 20th and 21st century. Though, in recent findings at the Icahn School of Medicine at Mount Sinai researchers found a way to make a natural defense mechanism fight and manage the previously seeming immortal bacterial infections. This natural defense mechanism is called cyclic oligonucleotide-based antiphage signaling system (CBASS). This defense mechanism is used by certain bacteria, like E.Coli, to protect themselves from viral attacks. The researchers used the CBASS-associated protein 5 (CAP 5) to understand how it could potentially be used to control bacterial infections. CAP 5 becomes activated by cyclic nucleotides to destroy the bacterias own DNA. In the past a multitude of other approaches have been tested including modifying existing antibiotics, creating new antibiotics, and also finding different ways of delivering these medications to the system. Though this potential solution to ARB still needs to be tested on more varieties of bacteria, it is a big stepping stone towards an answer of how to tame these bacteria. 

    This topic of antibiotic resistance is very intriguing to me for the fact that most people are severely undereducated in the way that antibiotic drugs work and how the bacteria they are fighting can become resistant. The importance of discovering a way to treat ARB is vital for the prevention of the spread of viruses in not only our country but across the globe, and the fact that these researchers from Mount Sinai have found a minimally invasive way of doing so by using naturally occurring mechanisms in the body is very intriguing. 

Sources: 

 1. https://www.sciencedaily.com/releases/2024/02/240206183543.htm

 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854991/

Artificial Life Form Given "Synthetic DNA"

Scientists have created an artificial form of E. coli based on entirely synthetic DNA.

    Scientists in the UK have created an artificial life form called "Syn61", a form of bacteria that has a completely redesigned 4 million letter genome. This feat can help pave the way for designer bacteria capable of manufacturing new proteins, drugs, and other materials. The DNA was ordered in short sequences, then assembled into longer sequences in yeast cells via cellular machinery. These yeast cells produced segments of DNA measuring 500,000 letters long. After each of these segments were tested in partially synthetic bacteria, the 8 segments were combined to create Syn61.

      Jason Chin, the head of this project also took the liberty to correct errors in the synthesis of this bacteria, only 4 total letters. In addition to this, Dr. Chin along with colleague Julius Fredens, decided to remove some codon duplications in the bacteria genome. There are 64 possible codons that can be arranged from A G C and T, however they only code for 20 amino acids, meaning multiple codons can code for the same amino acid. Chin and his team believe that reducing the number of codons can increase the bacterias efficiency. Syn61 gets its name from the fact that only 61 of the 64 possible codons are used by the cell. The three left over codons can now be "reassigned" to non-naturally occurring amino acids, which could bring a different chemistry to the cell. The number of codons needed was also reduced to improve efficiency. One way of achieving this was to use less "stop codons" (UAA, UGA, UAG) which can also potentially increase the efficiency of Syn61. These efficiency improvement techniques will be quite useful once bacteria can be synthesized for the sole purpose of creating drugs and other useful biochemical materials. The team also took further measures to remove material in the cell that was no longer needed, such as tRNA of the deleted codons.

     Syn61 has shown to grow roughly 60% slower than E. coli, which could suggest that the removed duplicate codons may actually have some importance. Nonetheless Syn61 is alive and reproducing despite having every gene on its singular chromosome altered. Another interesting finding is that the altered genetic code provides resistance to a wide variety of viruses simply because Syn61 lacks the tools to translate or integrate viral DNA, which could pave the way in creating virus resistant industrial microbes, plants/crops, and even human cells. Dr. Chin says they have not yet attempted to modify the virus in this capacity to be virus specific, but it is "high on his to-do list."

    I found this article interesting because the creation of this microbe is a big step forward in synthetic biology. As more becomes known about this procedure we may be able to give ourselves immunity to certain viruses by receiving DNA specific to anti-viral materials. I also had not thought about the idea of "bacteria farming", in creating bacteria to produce a useful material.


https://www.bbc.com/news/science-environment-48297647?intlink_from_url=https://www.bbc.com/news/topics/c40rjmqdw54t/genetics&link_location=live-reporting-story

Cell editors correct genetic errors

In an article published by Science Daily, scientists studying RNA editing have decided to turn to the professionals for help. Editing proteins known as PPR are masters in the art of RNA modification. In plants much of the genetic material contains small errors affecting the DNA in the mitochondria of the cells. But rather than changing the DNA (the actual building blueprints.) these editors act as proofreaders. Going over the RNA and proofreading for any mistakes. Since each editor can usually only recognize one specific error, most plants can have upwards of 500 different proof readers. Researchers curious to see how these whether these editors work alone, or if they need help decided to insert the PPR into E. coli. The assumption of most researchers was that the PPR locate errors and then call upon an RNA correction fluid, an enzyme called cytidine deaminase for help. However, what they discovered was that some PPR proteins have a certain sequence of amino acids at their end which are known to theoretically act as cytidine deaminase. It’s as if they carry their own vial of correction fluid, ready to correct any errors on the spot. 

The question is, why did this develop over the course of evolution. One theory suggests that the RNA editing may allow plants to collect mutations. With so many different combinations of changes that individually could be harmful or even fatal, but together could provide a survival advantage for the plant. Discoveries like these pave the way for amazing possibilities in the now not so distant future. One-day RNA editing will be used to cure diseases that today’s medicine simply cannot cure and treatments cannot help. The future of medical science may very well depend on genetics.

Using E.Coli to find cancer promoting proteins in humans

           Cancer results from the overproduction of mutations in the cell, which proceeds in the damage of the DNA. There are external events such as smoking and sunlight that damages DNA, but it is mostly an internal occurrence. A study conducted in BaylorCollege of Medicine and the University of Texas of Austin was proceeded to determine proteins that are cancer-promoting by using the bacteria E.coli as a model. Due to the bacterium E.coli having similar biological process with humans, Rosenberg—the leader of Cancer Evolvability Program—set out to uncover proteins that cause damage in the DNA in ways that can eventually lead to cancer.

            The team genetically modified E.coli to over express 4,000 bacterial genes. When the protein overproduction then turned fluorescent red this showed how it was associated to DNA damage. It was founded that the DNA that was damaged were not directly related to the DNA, but instead the transport of molecules across the cell membrane. It showed that the overproduction of E.coli proteins not only caused damage to the DNA but increase of mutations.

            This research can tell be used to further broaden our information in how there is many different ways that DNA can be damaged. By researching more in this topic we can then find ways to prevent or slow down ways of those that causes cancer. There could also be ways to protect our genomes from being harmed.

Scientists direct bacteria with expanded genetic code to evolve extreme heat tolerance

In recent years, scientists have engineered bacteria with expanded genetic codes that produce proteins made from a wider range of molecular building blocks, opening up a promising front in protein engineering.

Thermophiles, or thermophilic bacteria, are a type of extreme bacteria (extremophiles) that thrive in temperatures above 131 degrees Fahrenheit (55 Celsius).

Exposing bacteria with an artificially expanded genetic code to temperatures at which they cannot normally grow, the researchers found that some of the bacteria evolved new heat-resistant proteins that remain stable at temperatures where they would typically inactivate.

The scientists started by tweaking the genome of E. coli so that the bacteria could produce the protein homoserine o-succinyltransferase (metA) using a 21 amino acid code instead of the common 20 amino acid code. Above that temperature, metA begins to inactivate and the bacteria die. At this point, they let natural selection work. Heating the bacteria to 44 degrees Celsius, which is a temperature at which this bacteria cannot survive, the scientists put selective pressure on the bacteria population. As expected, some of the mutant bacteria were able to survive beyond their typical temperature ceiling, thanks to possessing a mutant metA that was more heat stable, all other bacteria died.

The researchers then identified the specific genetic sequence change that resulted in the mutant metA and found it was due to the unique chemical properties of one of their noncanonical amino acids that laboratory evolution exploited in a clever way to stabilize the protein.

Source: 

https://www.sciencedaily.com/releases/2018/11/181128082729.htm  Science Daily 

https://sciencing.com/examples-heatresistant-bacteria-20175.html  Heat-Resistant Bacteria

These Bacteria Use New DNA Bases to Make a Protein Not Found in Nature

Researchers at Scripp's Research Institute have used semi-synthetic bacteria to incorporate unnatural bases in their genetic code, allowing them to make amino acids that code for proteins that do not exist in nature. These two new bases were made using chemicals called dNaM and dTPT3 and were named X and Y. E.coli was first used to copy the unnatural bases and only recently were they able to be stored and passed on to daughter cells. The interesting thing about these new bases is that the RNA was able to transcribe them and incorporate unnatural amino acids that would code for a protein. This ability was used to create an alternative green fluorescent protein. This constructed protein was not functionally different from the original, however the new base pairs contributed to every stage of recovering information from the genetic code and using it to build proteins. Researchers hope to use this new technology in medicine to rework a molecule.

https://singularityhub.com/2017/12/07/these-bacteria-use-new-dna-bases-to-make-a-protein-not-found-in-nature/

http://www.iflscience.com/plants-and-animals/scientists-describe-potential-new-addition-dna-code/