Project description:The increasing antibiotic resistance of Klebsiella pneumoniae poses a serious threat to global public health. To investigate the antibiotic resistance mechanism of Klebsiella pneumonia, we performed gene expression profiling analysis using RNA-seq data for clinical isolates of Klebsiella pneumonia, KPN16 and ATCC13883. Our results showed that mutant strain KPN16 is likely to act against the antibiotics through increased increased butanoate metabolism and lipopolysaccharide biosynthesis, and decreased transmembrane transport activity.
Project description:Bacterial persister cells are phenotypic variants of regular cells that are tolerant to antibiotics. Analysis of clinical isolates of M. tuberculosis showed that strains vary substantially in their tolerance to antibiotics. The level of persisters was very high is some isolates, suggesting that these are hip mutants. We investigated gene expression differences in eight clinical isolates, four of which we characterized as high-persister strains and four as low-persister, or regular, strains. Comparison of gene expression patterns may provide clues as to the genetic mechanisms underlying persister formation.
Project description:The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae represents a major public health concern, primarily driven by its ability to evade a wide range of antibiotics. Despite extensive genomic studies, proteomic insights into antibiotic resistance mechanisms remain scarce. Here, we employed a data-independent acquisition (DIA)-based quantitative proteomics approach to investigate proteomic differences between 87 MDR and 20 antibiotic-sensitive K. pneumoniae clinical isolates. A total of 3,380 proteins were identified, with 896 showing significant differential expression. MDR isolates exhibited increased expression of efflux pumps, beta-lactamases, and transcriptional regulators, while proteins associated with glycerolipid metabolism and transport were enriched in sensitive strains. To validate our findings, an independent cohort of 10 MDR and 11 sensitive isolates was analyzed. Key biomarkers identified in the discovery cohort, including pyruvate decarboxylase and aldehyde dehydrogenase, were validated with high discriminatory power (AUC > 0.85) in the validation cohort. These findings provide novel insights into the molecular mechanisms of antibiotic resistance and identify promising biomarkers for diagnosing MDR K. pneumoniae, offering potential avenues for therapeutic intervention.
