Wednesday, January 27, 2021

Immuno-antibiotics: A New Frontier in the Fight Against Antimicrobial Resistance

Good news! A new class of antibiotics has been developed! The race for the cure!

"... the many antibiotic misuses and over-uses that have led to the development and spread of antimicrobial resistance (AMR), one of the greatest threats to human health of our time. And one of the most under-reported. ... Almost a century after the discovery of penicillin, an estimated 700,000 people die each year due to antibiotic-resistant infections such as tuberculosis and malaria ...
Not to mention the economic burden to patients and the health care system. In 2006, hospital-acquired sepsis and pneumonia cost the U.S. health care system more than $8 billion. ...
In the last two decades, only a few new antibiotics have been approved for clinical use and resistant bacteria have already emerged against these new drugs. ...
The new compounds, named immuno-antibiotics, kill bacteria by blocking a metabolic pathway that is essential for them to grow and survive. Though at the same time, these drugs potently activate a subset of T cells involved in immune responses to a wide variety of viral and bacterial infections, adding a second line of attack.
When tested on patient-derived, drug-resistant bacteria and in preclinical models of infection, immuno-antibiotics outperformed the current best-in-class antibiotics.
Creating a synergy between the direct killing of antibiotics and the natural power of the immune system, immuno-antibiotics have the potential to represent a milestone in the fight against AMR."

"... Isoprenoids are vital for all organisms, in which they maintain membrane stability and support core functions such as respiration. IspH, an enzyme in the methyl erythritol phosphate pathway of isoprenoid synthesis, is essential for Gram-negative bacteria, mycobacteria and apicomplexans ...After modification of these compounds into prodrugs for delivery into bacteria, we show that they kill clinical isolates of several multidrug-resistant bacteria—including those from the genera Acinetobacter, Pseudomonas, Klebsiella, Enterobacter, Vibrio, Shigella, Salmonella, Yersinia, Mycobacterium and Bacillus—yet are relatively non-toxic to mammalian cells. Proteomic analysis reveals that bacteria treated with these prodrugs resemble those after conditional IspH knockdown. Notably, these prodrugs also induce the expansion and activation of human Vγ9Vδ2 T cells in a humanized mouse model of bacterial infection. The prodrugs we describe here synergize the direct killing of bacteria with a simultaneous rapid immune response by cytotoxic γδ T cells ..."

Immuno-antibiotics: A New Frontier in the Fight Against Antimicrobial Resistance

Here is the underlying research paper:

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