Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1100205 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28680807_1.fastq.gz | Fastqsanger.gz | |||
| SRR28680807_2.fastq.gz | Fastqsanger.gz | |||
| SRR28680808_1.fastq.gz | Fastqsanger.gz | |||
| SRR28680808_2.fastq.gz | Fastqsanger.gz | |||
| SRR28680809_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Klebsiella pneumoniae poses a significant global health threat primarily attributable to its pronounced resistance. Here, we report an in vitro acquired resistance analyses of K. pneumoniae to the combination of amikacin and polymyxin B. We found some differentially expressed genes associated with the resistome of K. pneumoniae. The main differences were found in the genes aphA, asmA, phoP, and in the arn operon. Once these genes are related to modification in lipopolysaccharides, aminoglycosides and in the membrane structure, the mechanisms associated with them can justify the resistance acquisition to amikacin and polymyxin b.
2024-04-26 | GSE264574 | GEO
Project description:The emergence and spread of polymyxin resistance, especially among Klebsiella pneumoniae isolates threaten the effective management of infections. This study profiled for polymyxin resistance mechanisms and investigated the activity of polymyxins plus vancomycin against carbapenem- and polymyxin-resistant K. pneumoniae.
2023-10-13 | PXD045685 | JPOST Repository
Project description:Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.
2022-04-11 | PXD018528 | Pride
Project description:The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum -lactamase (ESBL)-producing bacteria is a critical threat to human health, and new treatment strategies are urgently required. Here, we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including the less-toxic next-generation polymyxin derivative, FADDI-287. We were unable to select for mutants resistant to PBT2 + FADDI-287 in polymyxin resistant E. coli containing a plasmid-borne mcr-1 gene or K. pneumoniae carrying a chromosomal mgrB mutation. Using a highly invasive K. pneumoniae strain engineered for polymyxin resistance through mgrB mutation, we successfully demonstrated the efficacy of PBT2 + FADDI-287 in vivo for the treatment of Gram-negative sepsis. These data present a new treatment modality to break antibiotic resistance in high priority polymyxin-resistant Gram-negative pathogens.
2020-07-01 | GSE153553 | GEO
Project description:The emergence of colistin resistance in carbapenem-resistant and extended-spectrum ß-lactamase (ESBL)-producing bacteria is a significant threat to human health, and new treatment strategies are urgently required. Here we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in several polymyxin-resistant, ESBL-producing, carbapenem resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including a ‘next generation’ polymyxin derivative, FADDI-287. To gain additional insight into the potential mechanism of action of PBT2, we analyzed the transcriptome of K. pneumoniae and E. coli in the presence of sub-inhibitory concentrations of PBT2. Treatment with PBT2 was associated with multiple stress responses in both K. pneumoniae and E. coli. Significant changes in the transcription of transition metal ion homeostasis genes were observed in both strains.
2019-06-13 | GSE132637 | GEO
Project description: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.
2021-11-25 | PXD028544 | Pride
Project description:Polymyxin B (PB) is introduced into the clinic as the last-line therapy against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Unfortunately, increased resistance to PB in <i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) has threatened global health. Resistance of <i>K. pneumoniae</i> to PB was induced by passaging in serial concentrations of PB and determined by microbroth dilution method. Growth characteristics of induced strains including growth curve, reversibility of resistance, and biofilm formation (crystal violet staining method) were measured. This study employed TMT-labeled quantitative proteomics and LC-MS/MS metabolomics analysis to investigate the key biological processes associated with PB resistance in <i>K. pneumoniae</i>. A total of 315 differentially expressed proteins (DEPs) were identified, of which 133 were upregulated and 182 were downregulated in the PB-resistant <i>K. pneumoniae</i>. KEGG enrichment analysis revealed that the DEPs were mainly involved in ATP-binding cassette (ABC) transporters and cationic antimicrobial peptide (CAMP) resistance. Proteins related to central carbon metabolism were inhibited in the PB-resistant <i>K. pneumoniae</i>, but proteins mediating LPS modification were activated. Transcriptional levels of CAMP resistance-related proteins were significantly different between PB-susceptible and -resistant <i>K. pneumoniae</i>. PB treatment led to an increase in reactive oxygen species (ROS) levels of <i>K. pneumoniae</i>. Metabolomics data demonstrated that 23 metabolites were significantly upregulated in PB-resistant <i>K. pneumoniae</i> and 5 were downregulated. The differential metabolites were mainly lipids, including glycerophospholipids, sphingolipids, and fatty acids. Exposure to PB resulted in increased level of phospholipid transport gene <i>mlaF</i> in <i>K. pneumoniae</i>. Our study suggested that membrane remodeling and inhibited central carbon metabolism are conducive to the development of PB resistance in <i>K. pneumoniae</i>.
2022-03-04 | MTBLS4132 | MetaboLights
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.
2023-04-18 | GSE229867 | GEO
Project description:Klebsiella pneumoniae is an antibiotic-resistant bacteria associated with severe infections, which has led to the search for new antimicrobial drugs to face these infections. Antimicrobial peptides (AMPs) are antimicrobials that exert anti-K. pneumoniae activity. Consequently, AMPs have been explored as a therapeutic option. However, similarly to other antimicrobials, K. pneumoniae can develop resistance against AMPs, although it is less frequent. Therefore, understanding the resistance mechanisms developed by K. pneumoniae against AMPs could aid in the design and development of more effective AMPs. This study aimed to identify via a label-free quantitative proteomic approach the resistance mechanisms involved in the resistance response of K. pneumoniae against the AMP PaDBS1R1.
2024-01-26 | PXD033020 | Pride