Singapore Scientists Develop Drug Delivery Microbe That Travels Up the Nose

The Blood-brain barrier(BBB) is layer of protective cells which line the circulatory system connected to the central nervous system which regulates what can and cannot enter. This functions to ensure that dangerous microbes and other dangers do not pose a threat to the brain and central nerves which are imperative to life. Despite this robust security system, it has one flaw... the nasal cavity. Microbes which are capable of navigating to the central nervous system nasally via the olfactory nerve are able to bypass the blood brain barrier and cause havoc to human health. However, scientists had realised this pathway could be critical to drug delivery bypassing the liver and BBB and began to experiment with intranasal drug delivery. Researchers at the National University of Singapore have taken this concept a step further and have developed microbes to deliver drugs directly into the nervous system via olfactory nerves.

The binding of the microbe to olfactory sites and

the movement of drugs(+) to the CNS via the olfactory nerve.

        

The BBB and liver are major obstacles in drug effectiveness, where their protective and selective nature prevents many drugs from being absorbed to their fullest potential. The researchers identified a myriad of nasal bacteria as candidates for this experiment, and ultimately decided upon Lactobacillus plantarum due to it's affinity for olfactory binding sites. The microbes were dyed to create fluorene for easier tracking, and then deployed into rats for live testing. The microbes remained in the nasal cavity while their drug payloads were diffused across the olfactory pathway into the central nervous system. The microbe underwent numerous edits via transformation in order to maximise olfactory binding and drug delivery, and the result was that the microbe administered drugs remained longer than those administered simply intranasally. While future studies and testing are needed to ensure that this method is safe, it is nonetheless a fascinating method of drug delivery and medical science. 

Sources:

https://phys.org/news/2025-02-bloodbrain-barrier-payload-bacteria.html

https://www.cell.com/cell/fulltext/S0092-8674(25)00046-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425000467%3Fshowall%3Dtrue        

https://pubmed.ncbi.nlm.nih.gov/22465159/

 

Designing and Programming Living Computers

 

    Graduate students and researchers from Technion and MIT collaborated to produce cells designed to perform computations similar to artificial neural circuits as explained in this article. A plasmid was inserted into a cell, acting as an artificial neural network. This was made possible by altering the plasmid’s genes, giving the plasmid the ability to activate and deactivate those genes due to stimuli. This is similar to how computer code works. Computer code consists of 0/1 switches, and the combination of those switches allows for different functions to be performed. The presence or absence of a molecule in a cell can act as a switch and perform similar functions. A cell can then be “programmed” to perform a function or set of functions such as the OR or AND functions. Artificial intelligence algorithms were also used to reduce the time and cost of genetic modifications to bacterial cells, making this technology more accessible. This technology is in a very early stage but has shown great potential to improve the dosage and effectiveness of cancer immunotherapy and diabetes drugs amongst other things.

Green Fluorescent Poop and Gut Inflamation

Inflammatory bowel diseases researchers hope to test for using genetically modified bacteria (File:Crohn's Disease vs Colitis ulcerosa.svg, Retrieved from Wikimedia Commons)

At the moment, monitoring the human digestive tract is a difficult task; however, the health of the digestive tract is important to one's overall health. In the quest to find better methods of testing for inflammatory bowel diseases (such as the ones pictured above), researchers from Rice University worked to edit Escherichia coli bacteria--a common, well-studied intestinal microbe--for this purpose. First, they worked to isolate genes that allow for the detection of sulfur compounds linked to inflammation. They then inserted this gene along with that of green fluorescent protein and tested it in healthy mice and in mice with inflammation of the bowels. Analysis of the excrement for green fluorescent protein showed that mice with inflammation of the bowels expressed the protein while healthy mice did not. The researchers hope to apply this in humans in the form of an easy, take-home medical test.

This article is an application of techniques done in lab with plasmid DNA and helps further emphasize the versatility of using plasmids to accomplish a variety of tasks.

Article from which post was based on
Original Published Journal Article

How Bacteria Resist Antibiotics in Hospitals

Scientists have discovered why antibiotic-resistant bacteria thrive in hospitals.  By using advanced DNA sequencing of samples from over 1,000 patients, researchers were able to identify antibiotic-resistant genes.  This was possible as they were able to see the complete genome of bacteria samples.  Circular DNA known as plasmids appear to be the center of the issue.  Plasmids easily enter bacteria and have the ability to move from one bacteria to another.  This study indicates that some plasmids carry a gene responsible for making bacteria drug-resistant.  Plasmids are able to multiply independently and can integrate their DNA with the DNA of bacteria.  Scientists have found that plasmids containing the gene capable of inactivating certain antibiotics can be transferred to bacteria of various classifications.  Dr. Tara Palmore, an infection control specialist for the U.S. National Institute of Health and co-author of this study stated, "The plasmids we are talking about carry an antibiotic-resistant gene to a class of antibiotic called carbapenems."  The carbapenem class of antibiotics are essentially antibiotics of last resort.  Dr. Marc Siegel, an associate professor of medicine at NYU Langone Medical Center stated, "Carbapenems are the best we have. So if you've got carbapenem resistance, there is nowhere else for us to go.  We don't have a secret treatment up our sleeves."  

The image above displays the serious threat that 

antibiotic-resistant bacteria pose to humans.  

According to the study, carbapenem-resistant Enterobacteriaceae (CRE) are bacterial pathogens that pose an alarming threat to hospitalized patients.  The occurrence of CRE has quadrupled in the United States in the last ten years. Researchers claim that CRE are resistant to most, if not all antibiotics.  A death rate of 40-80% from infection has been reported.  According to the U.S. National Institute of Health, over the past two years, ten patients have been identified as having resistance to carbapenems.  Although patients who contain this bacteria may not be sick themselves, they have the ability to pass the drug-resistant bacteria to others.  Dr. Julie Segre, chief investigator at the U.S. National Human Genome Research Institute and co-author of this study stated, "We are trying to reinforce the message that these drug-resistant bacteria can't become so prevalent that we can no longer control them."  

Ultimately, drug companies need to manufacture new antibiotics in which doctors need to use more cautiously.  Hospitals also need to do a better job of disinfecting facilities.  The correlation between the use of antibiotics and the increasing level of antibiotic- resistant bacteria is extremely interesting. In particular, this article caught my eye, as I always read how important it is for medical personnel to be careful when prescribing antibiotics.  Antibiotics are often prescribed during unnecessary circumstances in which over usage leads to ineffectiveness.  The article supports that theory due to bacteria forming resistance over time to even the most potent antibiotics available in the world today.


[1] Article: http://health.usnews.com/health-news/articles/2014/09/17/researchers-discover-how-bacteria-resist-antibiotics-in-hospitals
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