Immunity system complexity: battling Pseudomonas (Introduction)

by David Turell , Monday, November 25, 2024, 18:09 (3 hours, 39 minutes ago) @ David Turell

It has a way of dampening the immune system:

https://www.the-scientist.com/pseudomonas-bacteria-escape-immunity-by-disrupting-energy...

"In a recent publication in eLife, Harvard University molecular microbiologists Laurence Rahme and Arijit Chakraborty found that these bacteria release a chemical that inhibits energy generation in the mitochondria of macrophages, thus dampening the immune response.4 This work identified a new tactic that P. aeruginosa uses to subvert host immunity, and it intimated a new approach for treating the recalcitrant infection.

"One of the chemicals produced by Pseudomonas, called 2-aminoacetophenone (2-AA), is a useful biomarker for Pseudomonas infections in the clinic, but many of its functions, including its effects on innate immune cells, remain unexplored. Previously, the Harvard researchers found that macrophages don’t engulf and dispose of P. aeruginosa—an energy intensive process—in the presence of 2-AA.6 In the present study, they explored which mechanisms 2-AA might use to interfere with macrophage functions, focusing on how this molecule dampens macrophage bioenergetics.

"The team discovered that laboratory cultures of mouse macrophages inoculated with 2-AA produced less adenosine triphosphate (ATP), the molecule that cells use as an “energy currency” to fund energy-demanding biochemical reactions. This confirmed their suspicion that 2-AA dampens energy production in the cell. However, multiple pathways produce ATP. Since some pathways produce more ATP than others, they had to pinpoint the one 2-AA blocks to work out the magnitude of its impact.

"There are two main pathways that cells use to convert glucose into energy. The first is glycolysis, which occurs in the cytoplasm and produces two molecules of ATP per molecule of glucose. Pyruvate, the breakdown product of glycolysis, is then imported into the mitochondria where it fuels other energy-generating pathways, namely the Krebs cycle and oxidative phosphorylation. These produce approximately 30 additional ATP copies. Since only oxidative phosphorylation consumes oxygen, the researchers conducted a Seahorse assay to measure oxygen uptake by the cells using a probe that fluoresces in the presence of this gas molecule.9 Oxygen consumption dropped in cells exposed to 2-AA, revealing that the more-profitable energy-generating pathway crashed.

***

"As Pseudomonas bacteria grow increasingly resistant to antibiotics, researchers need to develop different types of therapeutics to treat them. Kayeen Vadakkan, a microbiologist at St. Mary’s College, Thrissur who was not involved with the work, suggested that 2-AA could serve as a new bull’s eye that drugs could target. “We can complement our immune system,” he said, proposing that drugs that block 2-AA’s effects could give macrophages a boost. Rahme’s laboratory is working on this therapeutic approach. “We’re very excited because the inhibitor of MvfR that we developed is working pretty well,” she said, referring to further research not included in this study. However, more research must take place to assess its efficacy and safety before it can be used in the clinic.

"Besides blocking 2-AA to fight bacteria, researchers could theoretically harness it to stave off autoimmune diseases. In some disorders, such as rheumatoid arthritis and lupus, overactive macrophages exacerbate inflammation.12 “2-AA is a molecule which is anti-inflammatory in nature,” Chakraborty said, suggesting that it may have potential as an immunosuppressive drug."

Comment: Pseudomonas is a tough nasty bug. This exciting research in finding ways to fight it. Of course dhw will point out God allowed this to exist. Iv don't know why, but here we see humans taking up the battle because we have the God-given mental capacity for it.