Project description:Antimicrobial resistance (AMR) is an increasing challenge for therapy and management of bacterial infections. Currently, antimicrobial resistance detection relies on phenotypic assays, which are performed independently of species identification. On the contrary, phenotypic prediction from molecular data using genomics is gaining interest in clinical microbiology and might become a serious alternative in the future. Although, in general protein analysis should be superior to genomics for phenotypic prediction, no untargeted proteomics workflow specifically related to AMR detection has been proposed so far. In this study, we present a universal proteomics workflow to detect the bacterial species and antimicrobial resistance related proteins in the absence of secondary antibiotic cultivation in less than 4 h from a primary culture. The method was validated using a sample cohort of 7 bacterial species and 11 AMR determinants represented by 13 protein isoforms which resulted in a sensitivity of 92 % (100 % with vancomycin inference) and a specificity of 100 % with respect to AMR determinants. This proof-of concept study demonstrates the high potential of untargeted proteomics for clinical microbiology.
2021-11-25 | PXD022425 | Pride
Project description:Network program on AMR, superbugs and One health
Project description:Tuberculosis (TB) is an ancient disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). The rise of antimicrobial resistance (AMR) threatens to bring Mtb to the forefront of bacterial pathogens as the current treatments are increasingly becoming ineffective. Understanding the development of AMR and the virulence processes of Mtb is crucial for the identification of new drug targets and the rational design of anti-TB treatments. One of the established mechanisms of resistance is through the function of efflux proteins, which are transmembrane transporters that bind and remove antibiotic molecules out from the cell. Here, we determine the role of Rv3728, a major facilitator superfamily (MFS) efflux pump protein, which also predicted to bind 3',5'-cyclic adenosine monophosphate (cAMP). Using bioinformatic tools and cAMP binding assay, we confirm that Rv3728 binds to cAMP and identified E597 and R606 as important residues involved in binding. Although Rv3728 deletion has no impact on bacterial resistance and tolerance to different antibiotics, it affects membrane permeability and alters the acylation profile of phosphatidyl-myo-inositol mannosides lipids.
2024-06-10 | GSE268977 | GEO
Project description:Canadian MetaMicroBiome Initiative samples from
Project description:Antimicrobial resistance (AMR) is one of the major challenges that humans are facing this century. Understanding the mechanisms behind the rise of AMR is crucial to tackle this global threat. Among the triggers of phenotypic antimicrobial resistance, the contribution of transition metals has been understudied in Mycobacterium abscessus (Mabs), a fast-growing non-tuberculous mycobacterium known for its extreme AMR levels. Deeper understanding of the effects of transition metal ions will be beneficial for our knowledge in AMR and the discovery of potential therapeutic targets. Here, we investigated the impact of transition metal ions, nickel, cobalt and copper on the physiology and drug susceptibility of Mabs.