How antibiotic resistant microbes protect themselves from attack of body's defenses

Klebsiella pneumoniae can cause infections that are becoming untreatable due to the lack of effective antibiotics.

More than five million deaths a year are caused by the disease. Three million routine operations could become life threatening due to the lack of effective antibiotics.

The findings, published in Cell Reports, represent a step change in the fight against antibiotic resistant infections and were led by researchers from the Trinity Biomedical Sciences Institute at Trinity College Dublin.

The research shows that Klebsiella hijacks a cell's SARM1 to limit inflammation. SARM1 has been shown to be involved in neurological diseases.

Researchers have shown that Klebsiella causes the expression of SARM1 in macrophages, a type of white blood cell. Macrophages killbacteria, remove dead cells, and stimulates the action of other immune system cells, to blunt inflammation and to survive inside, resulting in a protective niche to the action of antibiotics. One of the weaknesses of our defense was revealed by these findings.

Researchers have shown that the absence of SARM1 facilitates the clearance of Klebsiella without need of antibiotics. Anti ASMR1 drugs are being investigated to see if they can be used to treat Klebsiella infections alone or in combination with antibiotics.

The lead of the project, Professor Jose Bengoechea, is a world leader in the deadly Klebsiella pneumoniae infection.

Our research showed how deadly infections manipulate our cells for their own benefit, but it also showed a new target, SARM1, to combat these infections. Funding across the island of Ireland made it possible for this research to take place, as the recent Pandemic has shown to be of critical importance in public health.

The surprising and unexpected discovery that Klebsiella manipulates SARM1 to counteract host inflammation was made by Professor Andrew Bowie, Professor of Innate Immunology at Trinity College Dublin.

A major area of research interest to the UK and theBBSRC is AMR. It has significant societal implications and I'm pleased to see that a collaboration between the Science Foundation Ireland and theBBSRC has been able to discover a fundamental biological process that may translate into the reduced use of antibiotics. This is a positive outcome for both the U.K. Government and theBBSRC.

More information: Claudia Feriotti et al, Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity, Cell Reports (2022). DOI: 10.1016/j.celrep.2022.111167 Journal information: Cell Reports Citation: How antibiotic resistant microbes protect themselves from attack of body's defenses (2022, August 25) retrieved 25 August 2022 from https://phys.org/news/2022-08-antibiotic-resistant-microbes-body-defenses.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.