Discovering New Tuberculosis Drugs from Old Antibiotics

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Highlights:

• Tuberculosis can be treated effectively with the improved drugs by researching old antibiotic patterns of D-Cycloserine.
• Understanding and evaluating old antibiotics can create an effective approach in the field of drug research and development.
• Newer drugs are needed to stop the rising issue of antibiotic resistance which is a current scenario addressed worldwide.

Tuberculosis (TB) is considered to be one of the top ten cause of death globally. It is caused by a bacteria known as Mycobacterium tuberculosis which usually affects the lungs.

Tuberculosis is an air-borne disease which spreads when the TB patient coughs, sneezes or spits. It is found that nearly one-quarter of the world's population has latent TB which means they do not fall either ill or do not transmit the bacteria. People who are infected by HIV are at great risk of developing acting tuberculosis.

‘Drugs such as D-Cycloserine modified structurally as new chemical species treat microbial diseases such as Tuberculosis by acting at various bacterial targets with minimal adverse effects. This ends the nature of antibiotic resistance which may serve as effective drugs in future.’

Tuberculosis can be treated effectively as expected before, finds a new study conducted by Professor David Roper at the University of Warwick and Dr. Louis Pedro at Francis Crick Institute. The study was focused on the activity of D-Cycloserine at the two enzymatic levels. D-Cycloserine an old antibiotic, surprises the research team with its antibacterial activity by acting in two different ways.

D- Cycloserine activity at bacterial level

Cycloserine has a broad spectrum antibacterial activity, which is used as a second line therapy against drug-resistant tuberculosis usually in a combination of other tuberculosis treating agents.

Peptidoglycan is essential for the synthesis of the bacterial cell wall and D-cycloserine interferes with the bacterial cell wall synthesis mainly by inhibiting two enzymes such as D-alanine racemase and D-alanine-D-alanine ligase. These two different enzymes are responsible for building and maintaining the structural integrity of the bacterial cell wall.

D-Cycloserine binds to the D-alanine racemase and the formation of chemical group stops the microbial activity which is usually a normal pharmacological behavior. D-alanine-D-alanine ligase when binds to the drug D-Cycloserine produces a different chemical which is a breakthrough in the drug receptor theory.

D-Cycloserine by its chemically modified activity on the bacterial enzyme proves the drug a unique among the other antibiotics. By clearly analyzing the bacterial activity at the cellular level paves the way to develop more effective drugs in future. The puzzle of antibiotic resistance which is a current threat in the field of medicine can be easily solved by understanding such specified drug actions at the molecular or the cellular level.

Tuberculosis can be diagnosed by the following screening methods:

• Chest X-ray
• Skin test (Mantoux test)
• Tuberculosis Interferon Gamma release assays (IGRAs)
• TB culture test
• Serological test
• Sputum smear microscopy
• Fluorescent microscopy

Tuberculosis treatment schedule

Active tuberculosis can be treated with a WHO-approved standard 6-month course with 4 antimicrobial drugs. The treatment schedule consists of two-month intensive phase followed by four months continuation phase.

Two-months TB intensive phase includes the drugs such as Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. Streptomycin is also considered as a first line agent in treating tuberculosis. The four-months continuation phase includes the drugs such as Isoniazid and Rifampicin.

The pharmacological or the drug therapy should be supported by providing information to the patient about the disease, the control measures, and support from the healthcare worker. These efforts help the patient adhere to the treatment schedule properly.

References:

1. Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine - (https:www.nature.com/articles/s41467-017-02118-7.pdf)
2. About Tuberculosis - (http://www.who.int/mediacentre/factsheets/fs104/en/)
3. TB treatment - Curing TB, failure, relapse & recurrence - (https:www.tbfacts.org/tb-treatment/)

Source: Medindia

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