Mycobacterium tuberculosis:

More commonly referred to as “Tuberculosis” or just “TB”, there are an estimated 10 million new infections annually and approximately 1/5 of the human population, or 1.5 billion people, are thought to be latently infected globally. Each year there are approximately 2 million deaths due to TB, many of them due to drug-resistant infections.

The Pathogen

TB is a gram-indeterminate bacillus, but shares similarities with gram-positive bacteria. The bacterium is especially notable for its unique cell wall consisting of mycolic acids. Mycolic acids are thought to promote the virulence of M. tuberculosis, from physically impeding the activity of extracellular compounds, to directly modulating the host’s immune response. M. tuberculosis is an obligate pathogen, with no significant biological reservoir outside of humans, meaning it can not survive outside of human hosts. As a result, TB has mechanisms to create an ideal environment inside the phagosome of human cells where it can survive and multiply, like preventing phagosomes from fusing with lysosomes. The lysosome is where cells digest unwanted items, so by preventing this fusion, TB prevents it's own digestion. Since the human cell can't get rid of TB it instead encases it within a granuloma - a ball of immuno-cells - which stop TB from growing and switch it to the latent phase of infection. Patients with latent TB infections often show no outward signs of disease, but carry a high lifetime chance of reactivation - where TB grows, breaks out of the granuloma cell, and begins an active infection again.

Consumption = TB

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TB infections have plagued humans throughout much of our history with telltale signs observed in Egyptian mummies dating back to 2400 BC. The disease has gone through many names throughout human history from “phthisis” by ancient Greek writers, “schachepheth” in ancient Hebrew, to the “kings evil” in medieval Europe, and “consumption” in the 1800’s. TB is often mistakenly thought of as an “old world disease”, but TB infections continue to threaten humankind today. TB normally infects the lungs, leading to a bad lingering cough, pain in the chest, and coughing up blood or sputum (phlegm from deep inside the lungs). Other symptoms include weakness, fatigue, weight loss, loss of appetite, chills, fever, and sweating at night.


TB drug-resistance

Unlike most of the other MDR (multi-drug resistant) organisms that are threatening humankind, TB does not acquire its’ drug resistance from horizontal gene transfer. Instead, TB relies on its high intrinsic physical resistance mechanisms, its slow rate of growth, the protection afforded by its intracellular lifestyle, and a high propensity to develop genetic resistance mutations to protect it from antimicrobials. Effective therapeutic options are dwindling for TB infections, as highlighted by the decreasing success rate of the four-drug combination-therapy that has been utilized for TB patients since the mid-1970’s. Accordingly, 3% of new active infections are classified as MDR, and XDR TB (extensively drug resistant), comprised of strains that are resistant to all known antimicrobials, which have now been detected in multiple countries.

 
 

Utlizing Machine Learning in the fight against AMR

Using machine learning to study 1595 strains of M. tuberculosis, CHARM Investigators were able to correctly identify 33 known AMR genes and 24 potential new ones. This process has led to a computational platform that clinicians could use to manage treatment of their TB patients. 

Read the article from Nature Communications
Back to Leading AMR Pathogens