Category Archives: Analytical Chemistry

The Key to Treating Pneumonia can be Found in Soil?

Posted on March 27, 2020 by | Leave a comment

Can it really be that simple? Can the answer really be in the ground beneath our feet?

Source: Soil Science Society of America

Discovery of a gene cluster commonly found in soil-dwelling bacteria may be the key to treating anaerobic bacterial infections such as appendicitis and pneumonia. Researchers Jason B. Hedges and Prof. Dr. Katherine S. Ryan from the University of British Columbia have isolated the antibiotic compound azomycin from a biosynthetic gene cluster found in the bacterium Streptomyces cattleya.

With this information they believe it can lead to engineering bacteria to produce a new line of antibiotics.

What is a gene cluster?

The term gene cluster is moreso semantics to describe a group of genes that share a common phenomenon.

Originally, azomycin was isolated from a similar bacterium Streptomyces eurocidicus back in 1953 and became the blueprint to synthetic nitroimidazoles. 

“Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections”,[1] Hedges writes in his 2019 study. The most commonly used nitroimidazole, metronidazole, is an antibiotic used to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.[2] It is also on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.[3]

Figure 1: Molecular Structure of Nitroimidazole. Source: Sigma Aldrich

Despite its use in antibiotics for over 60 years, the incidence of nitroimidazole resistance in anaerobes remains low, making it an essential component of the antibiotic arsenal. [1,4]

Since the isolation of azomycin back in 1953, synthesis of nitroimidazoles were limited to synthetic routes, most commonly involving reactions of an imidazole with nitric acid and sulfuric acid. 

Using bioinformatics, however, in 2019 Hedges and Ryan were able identify a biosynthetic gene cluster in the same bacterium that makes penicillin,[5] Streptomyces cattleya. They were able to find that this gene cluster containing azomycin is widely distributed among soil-dwelling actinobacteria and proteobacteria.

Because of this they theorize that azomycin and other nitroimidazoles may be important factors in ecology.

What are bioinformatics?

Bioinformatics is the science of collecting and analyzing complex biological data such as genetic codes. As an interdisciplinary field of science, bioinformatics combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data

In addition to the isolation of azomycin in a gene cluster, Hedges and Ryan were able to perform in vitro analysis in order to understand the enzymatic steps that take the primary protein L-arginine to become azomycin. 

Source: Washington Post

Their work opens the door to biocatalytic methods to synthesize azomycin and other nitroimidazoles. They believe this discovery can “lead to the possibility of engineering bacteria to produce nitroaromatic compounds”.[1]

In other words, this may lead to stronger antibiotics immune to drug resistance.

References

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

The American Society of Health-System Pharmacists. Archived from the original on 6 September 2015. Retrieved 31 July 2015.

World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization

David I. Edwards, Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action, Journal of Antimicrobial Chemotherapy, Volume 31, Issue 1, January 1993, Pages 9–20, https://doi.org/10.1093/jac/31.1.9

Kahan, JS; Kahan, FM; Goegelman, R; Currie, SA; Jackson, M; Stapley, EO; Miller, TW; Miller, AK; Hendlin, D; Mochales, S; Hernandez, S; Woodruff, HB; Birnbaum, J (Jan 1979). “Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties”. The Journal of Antibiotics. 32 (1): 1–12

-Adrian Emata

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Posted in Analytical Chemistry, Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science

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Biosynthetic Pathway Found to Synthesize Anaerobic Antibiotics!

Posted on March 23, 2020 by | Leave a comment

Fig 1. Image of Azomycin. source

Scientists found the biosynthetic pathway to the Nitroimidazole Antibiotic Azomycin. A steppingstone towards the revolution of anaerobic bacterial infection treatments.

Scientists from the University of British Columbia found the biosynthetic pathway to the Nitroimidazole antibiotic Azomycin. The enzymatic mechanism from L-Arginine to Nitroimidazole has now been proved and present to the public. Their formal paper was published online on July 17th, 2019. Nitroimidazole is an essential component for the modern antibiotics, it is crucial to know its synthetic pathway for further pharmaceutical studies. The result of their study set the stage for further development of important anaerobic antibiotic Azomycin.

What is it? Why do we need to know about this?

Nitroimidazole is an essential antibiotic specifically to treat anaerobic bacterial infections. They are widely used to treat diseases such as Amoebiasis, Parasitic infections, skin infections, diarrhea and so on. The low redox potential of anaerobic bacteria cells allowed nitroimidazole to act as the electron sink and form the radical species. The resultant radical species would induce the bacteria cells’ death by damaging their DNA. Antibiotic is the most powerful “weapon” to fight against bacterial infections. However, according to the World Health Organization, there are more than 700000 people die every year due to antibiotic resistance. Despite the several decade’s usages of Nitroimidazole antibiotics, the drug resistance of it still remains low relatively. Thus, Nitroimidazole antibiotics are increasingly used to treat multi-drug resistant bacteria as well.

 

Previous research established that L-Arginine is converted to azomycin by 2-aminioimidazole. They determined that the intermediate of the reaction is 4-hydroxy-2-ketoarginine (2). Furthermore, they also observed the accumulation of pyruvate(3) side products and 2-aminoimidazole(5) from the intermediate(2). However, the actual enzymatic synthetic pathway has not been determined detailly yet. Jason and Katherine in the research group determined that PLP-dependent enzymes, RohP,RohR,RohQ and RohS plays esstential role in the catalytic pathway of the reaction. Researchers examined the in vitro activity of RohP, RohR, RohQ and RohS. They put in these enzymes separately and stepwise to different reactants. For example, in order to test whether RohR could catalyze a retro-aldol cleavage of 2 into 3 and guanidinoacetaldehyde (4), they added purified RohR instead of RohP. Then according to activity analysis and also the mass spectrum, the result shows that RohP yields a bigger portion of 2.

Fig 2. Reaction scheme from L-Arginine to Nitroimidazole. Source

Antibiotics are the most powerful “weapon” to kill bacteria in modern pharmaceutical studies. As early as in the 20th century, the observation of penicillin saved millions of people injured in the World War. Yet, the enormous benefits of antibiotics cause the consequences of drug-resistance. Azomycin, consider as a low-resistance antibiotic, it is crucial to understand its enzymatic reaction mechanism. Reaction mechanism allows scientist to have a more detail interpretation of the synthesis. It is crucial to find the catalytic cycle of the reaction, in order to allow scientists to develop and derive further study.

The study done by Jason and Katherine at the University of British Columbia provides the public with a steppingstone in future nitroimidazole anti-biotics study. Their study expanded people’s knowledge of the biosynthetic pathway to nitro-compounds. It also makes bacteria engineering to produce nitroaromatic compounds possible. This study will open the new door in enzymatic synthesis and biochemistry synthesis.

Cited article:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

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Inexpensive and rapid test to detect Lyme disease

Posted on March 16, 2020 by | 1 comment

A Great Challenge

Lyme disease is the most common vector-borne infectious disease in North America and Europe. Caused by the spirochete bacterium Borrelia burgdorferi, it is characterized by a rash in infected skin and leads to major symptoms if left untreated. Though many tests have been developed to diagnose this disease, the currently available tests are expensive and lack sensitivity (true positive rate) when it comes to the early stages of the infection.

 

Fortunately, a team of scientists from The University of California, Los Angeles, has recently developed a new inexpensive and trustful way of detecting this infection. They claim that this new procedure does not need previous training to be implemented, and that its sensitivity can be greater than 90%.

Figure 1: Lyme disease testing procedure. Adapted from ACSNANO

How does it work?

Figure 2: Illustration of the complexed reactions that lead to identification of the lyme disease. Adapted from ACSNANO

This novel test consists of a paper based multicomplex vertical flow assay, where small paper layers are covered in various disease-specific target proteins that interact with different antigens present in human samples. The protein-antigen interaction results in an observable change in colour. Upon the completion of the test, they generate a colour pattern that can be analyzed by a computer or even a smartphone. This allows possible diagnosis of the disease within minutes and increases specificity (true negative rate) and sensitivity in its early stages. The test has also been optimized with positive and negative controls to avoid false diagnoses, and it is enclosed in a 3D printed case for easy handling.

 

Major Improvements to Technology

Figure 3: Reported data on test sensitivity, specificity and Area Under the Curve. Adapted from ACSNANO

Previously used examinations could cost up to 400 USD per test, and their average time for diagnosis is currently over 24 hours. They also have very low sensitivity to the early stages of the disease, with values of less than 50% being reported. As mentioned by the authors, this assessment has a material cost of 0.42 USD per test which greatly reduces costs for diagnoses. They also report values of sensitivity of over 90% in early stages of Lyme disease and a specificity value of 87%. Nonetheless, this team of researchers have demonstrated the correct diagnosis of the disease in a matter of minutes making this process efficient, easy and available to the public at a reduced cost.

 

-Aron Engelhard

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Posted in Analytical Chemistry, Biological Chemistry, Chemistry News

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Enhancing Safety Gloves

Posted on March 1, 2020 by | 1 comment

Safety gloves do not protect you from every chemical or dangerous substance. The glove deteriorates and makes it easier for chemicals to penetrate through and onto the skin. One way to tackle this problem is by implementing a self-healing material, which can be used for rubber gloves.

Researchers at the Central Institute for Labour Protection in Poland tested  polyamide, cotton–polyamide, and cotton fabrics, onto methyl vinyl silicone rubber containing inorganic silsesquioxane, which are used for rubber gloves. Its resistance to chemical substances, abrasions, and punctures were analyzed. Using SEM, the surface is observed for any damages or self-healing behaviour for each rubber material containing each type of fabric.

A cross-section of a rubber material with textile reinforcements (Source: Irzmańska)

A test to determine the resistance of chemical substance with methyl vinyl silicone rubber with silsesquioxanes, and one coated with cotton was carried by using 2-propanol. This studied the breakthrough time of the 2-propanol through the 2 different materials at various conditioning times. The idea is to simulate the effectiveness of the self-healing mechanism.

Permeation times of 2-propanol into 2 different materials (Adapted: Irzmańska)

The data shows an increase in permeation time when coated with cotton, and when conditioned at 70 degrees Celsius for 24, 48, 72 hours. This means coating the material with textile reinforcements increases the resistance of chemical substances from penetrating. A similar trend was obtained when testing different textile compositions through puncture and abrasion tests.

The result concludes the effectiveness of the textile reinforcement in the self-healing process, qualitatively and quantitatively. This study brought improvements to lessen the stress chemists have on the quality of their own safety gloves. Safety gloves should never be a safety concern.

-Wilson Wong

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Revised: Effective Means of Diagnosing Alzheimer’s Disease

Posted on February 15, 2020 by | Leave a comment

Alzheimer’s disease is an incurable disorder that must be treated early and carefully. It is a fatal disease that needs more attention. Biomarker analysis can be a method to detect early signs of the disease, and carbon nanomaterials can be a tool for this method to be applied.

It is estimated that 5.5 million Americans, mainly affecting people over the age of 65, suffer from Alzheimer’s disease without a cure, and is rapidly increasing. This does not mean nothing can be done to help treat the disease.

Researchers at the University of Porto studied carbon nanomaterials and their biosensing applications to determine the biomarkers of Alzheimer’s disease. The study in 2019 urged the importance of biomarkers for indication of Alzheimer’s disease.

To enhance treatment for this disease, early diagnosis is necessary and requires a method of indication. The study focused on biomarkers of pre-clinical stages of Alzheimer’s. Stage 1 includes increased amyloid burden, stage 2 includes neuronal injury and evidence of neurodegenerative change, and stage 3 includes subtle cognitive decline. Although the biomarkers developed can provide good results, various criteria must be met.

Biomarkers of Alzheimer’s Disease (Source: Laurent Hemoye)

Another study mentions the ability to produce biosensors from nanomaterials mainly because of their electrochemical activity and biocompatibility. Carbon nanotubes display exceptional electronic properties, due to its high surface-to-volume ratio, and is most commonly used for biosensing. Graphene is also common, and can be functionalized by various functional groups to improve selectivity to biomolecules.

Structure of Nanotubes (Source: Carneiro et al.)

A demand for more research on developing credible biomarkers for Alzheimer’s disease is crucial for early diagnosis, as more studies show biosensing as a challenge. This could potentially enhance the understanding of the disease and invent a cure.

-Wilson Wong

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Effective Means of Diagnosing Alzheimer’s Disease

Posted on January 27, 2020 by | Leave a comment

Alzheimer’s disease is an incurable disorder and mainly affects people over the age of 65. It is a fatal disease that must be treated early and carefully. A new method to detect early signs of the disease is currently being investigated. Researchers at the University of Porto studied carbon nanomaterials and their biosensing applications to determine the biomarkers of Alzheimer’s disease.

A recent study in 2019 urged the importance of biomarkers for indication of Alzheimer’s disease. It is estimated that 5.5 million Americans suffer from Alzheimer’s disease without a cure, and is rapidly increasing. This does not mean nothing can be done to help treat the disease. To enhance treatment for this disease, early diagnosis is necessary and requires a method of indication. The study focused on biomarkers of pre-clinical stages of Alzheimer’s. Stage 1 includes increased amyloid burden, stage 2 includes neuronal injury and evidence of neurodegenerative change, and stage 3 includes subtle cognitive decline. Although the biomarkers developed can provide good results, various criteria must be met.

Biomarkers of Alzheimer’s Disease (Source: Laurent Hemoye)

Another study mentions the ability to produce biosensors from nanomaterials mainly because of their electrochemical activity and biocompatibility. Carbon nanotubes display exceptional electronic properties, due to its high surface-to-volume ratio, and is most commonly used for biosensing. Graphene is also common, and can be functionalized by various functional groups to improve selectivity to biomolecules.

Structure of Nanotubes (Source: Carneiro et al.)

A demand for more research on developing credible biomarkers for Alzheimer’s disease is crucial for early diagnosis, as more studies show biosensing as a challenge. This could potentially enhance the understanding of the disease and invent a cure.

-Wilson Wong

 

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