HEИндивидуална стипендия2023–2025

MAREE · Mechanisms of Antibiotic Recalcitrance in ESKAPE pathogens

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-07-01 → 2025-06-30
Финансиране от ЕС: 195 915 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите, чрез които бактерии като Enterococcus faecium оцеляват след антибиотично лечение, се анализират на ниво протеини. Разбирането на този процес помага да се ограничи връщането на инфекциите и развитието на още по-устойчиви щамове.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Mechanisms of Antibiotic Recalcitrance in ESKAPE pathogens

The discovery of antibiotics in the late 1920s was one of the biggest achievements in medicine. However, the rise of antimicrobial resistance (AMR) now threatens this progress. The World Health Organization (WHO) warns that by 2050, antibiotic-resistant infections could cause 10 million deaths per year and cost the global economy 1.2 trillion US dollars. A particular group of bacteria called ESKAPE pathogens—which include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species—are especially dangerous. These bacteria often cause hospital-acquired infections and have developed resistance to multiple antibiotics. One major problem is antibiotic (AB) recalcitrance—a situation where bacteria that seem sensitive to antibiotics survive treatment and cause the infection to return once the treatment ends. This contributes to the failure of antibiotic therapies and can lead to the development of even more resistant bacterial strains. Unfortunately, the biological mechanisms behind this phenomenon are still poorly understood. The MAREE project aims to understand how this recalcitrance works by focusing on two ESKAPE bacteria : Enterococcus faecium (Efm) and Enterobacter cloacae complex (Ecc) The overall biological question how these bacteria survive antibiotic treatment at the protein level, as proteins play a crucial role in changing the bacteria’s metabolism and helping them survive treatment. The project has three main goals: (i)identify the stress conditions and antibiotics that trigger recalcitrance and isolate specific subpopulation, (ii)analyze the proteins and phosphorylated proteins (those that regulate many cellular functions) involved in this state, (iii)test the role of key proteins through genetic modification and lab experiments, in collaboration with Prof. Helaine at Harvard Medical School. The expected outcome is a better understanding of how bacteria survive antibiotic treatments. This knowledge could lead to new targeted therapies to fight recurring infections and slow down the spread of antibiotic resistance.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Antimicrobial resistance (AMR) is the silent pandemic uprising for the past decades that challenges practitioners to everyday life. In this context, more and more infections have become harder to treat, even in absence of genetic markers for AMR. This phenomenon, called recalcitrance, is related to the ability of susceptible bacteria to overcome antibiotic treatment and to reinitiate infection contributing to antibiotic failures and resistance emergence. Previous studies have described the involvement of a phenotypic switch leading to recalcitrance but underlying mechanism remain poorly understood. ESKAPE (standing for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens are the most prevalent causative agents in common recurrent healthcare-associated infections as well as well-known for their multidrug resistant phenotype and are the best candidates to understand recalcitrance. Hereby, we propose to investigate two of them, E. faecium (Efm) and E. cloacae complex (Ecc) by studying the proteome involved in recalcitrance. To identify any protein and/or pathway of interest, we will (i) identify which stress and bactericidal antibiotic induce recalcitrance both in Efm and Ecc; (ii) evaluate proteome and phosphoproteome of isolated antibiotic-recalcitrant bacteria; and (iii) confirm functionality of candidate proteins/pathways by mutagenesis and phenotypic approaches (in vitro and in cellulo) with the expertise of Prof. Helaine at Harvard Medical School (HMS) in Boston (secondment). Finding potential protein targets can highlight new candidates to further develop new therapies to overcome the rising of AMR.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE RENNES · RennesКоординаторФранция
Harvard Medical School · BostonСъединени щати