Comparative proteomics demonstrates altered Metabolism pathways in cotrimoxazole-resistant and amikacin-resistant Klebsiella pneumoniae isolates

ABSTRACT: The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CR-KPN) infections have worsened the current situation worldwide. Clinically, cotrimoxazole (CTX) and amikacin (AMI) are considered to be the preferred drugs in the treatment of (CR-KPN). But for now, the extensive use of cotrimoxazole (CTX) and amikacin (AMI) During the course of treatment leads to the emergence of cotrimoxazole- and amikacin-resistant infections, which is of great clinical concern. Previous evidence has shown that bacteria with reduced metabolism tend to be resistant to antibiotics, however, the mechanism remains unclear. In the present study, proteomics was performed on the sensitive, cotrimoxazole-resistant, amikacin-resistant and cotrimoxazole/amikacin-both-resistant KPN clinical isolates, and 2266 proteins were identified in total by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. Further bioinformatic analysis showed down-regulation of tricarboxylic acid cycle pathway and up-regulation of alcohol metabolic or glutathione metabolism processes, which may contribute to ROS clearance and cell survival, in drug-resistant isolates. Finally, combined with minimum inhibitory concentration (MIC) of Amikacin and Cotrimoxazole on different KPN isolates, we identified nine proteins contributed mostly to such an alteration and the survival of bacteria under drug pressure, which could reveal novel mechanisms or pathways involved in drug resistance. These proteins and their pathways might be used as targets for the development of novel therapeutics against antimicrobial-resistant (AMR) infections.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Klebsiella Pneumoniae Atcc 43816

TISSUE(S): Cell Culture

SUBMITTER: jingbo qie  

LAB HEAD: jingbo qie

PROVIDER: PXD028544 | Pride | 2021-11-25

REPOSITORIES: Pride