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ABSTRACT:
PROVIDER: PRJNA612823 | ENA |
REPOSITORIES: ENA
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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:The study aimed to characterize plasmids mediating carbepenem resistance in Klebsiella pneumoniae in Pretoria, South Africa. We analysed 56 K. pneumoniae isolates collected from academic hospital around Pretoria. Based on phenotypic and molecular results of these isolates, 6 representative isolates were chosen for further analysis using long reads sequencing platform. We observed multidrug resistant phenotype in all these isolates, including resistance to aminoglycosides, tetracycline, phenicol, fosfomycin, floroquinolones, and beta-lactams antibiotics. The blaOXA-48/181 and blaNDM-1/7 were manily the plasmid-mediated carbapenemases responsible for carbapenem resistance in the K. pneumoniae isolates in these academic hospitals. These carbapenemase genes were mainly associated with plasmid replicon groups IncF, IncL/M, IncA/C, and IncX3. This study showed plasmid-mediated carbapenemase spread of blaOXA and blaNDM genes mediated by conjugative plasmids in Pretoria hospitals.
2019-10-17 | GSE138949 | 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:With the global increase in the use of carbapenems, several gram-negative bacteria have acquired carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is one of such notorious pathogen that is being widely studied to find novel resistance mechanisms and drug targets. These antibiotic-resistant clinical isolates generally harbor many genetic alterations, and identification of causal mutations will provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance, in which mutated genes that also show significant expression changes among their functionally coupled genes become more likely candidates. For network-based analyses, we developed a genome-scale co-functional network of K. pneumoniae genes, KlebNet (www.inetbio.org/klebnet). Using KlebNet, we could reconstruct functional modules for antibiotic-resistance, and virulence, and retrieved functional association between them. With complementation assays with top candidate genes, we could validate a gene for negative regulation of meropenem resistance and four genes for positive regulation of virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antimicrobial resistance and virulence of human pathogenic bacteria with genomic and transcriptomic profiles from antibiotic-resistant clinical isolates.
2018-06-10 | GSE115539 | GEO
Project description:Proteomic analysis of carbapenem-resistant Klebsiella pneumoniae exposure to tigecycline and aminoglycosides
2022-01-17 | PXD031030 | iProX
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: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:Carbapenem-resistant Klebsiella pneumoniae classified as multilocus sequence type 258 (ST258)are a problem in healthcare settings in many countries globally. ST258 isolates are resistant tomultiple classes of antibiotics and can cause life-threatening infections, such as pneumonia andsepsis, in susceptible individuals. Treatment strategies for such infections are limited. Hence,understanding the response of K. pneumoniae to host factors in the presence of antibiotics couldreveal mechanisms employed by the pathogen to evade killing in the susceptible host, as well asinform treatment of infections. Here, we investigated the ability of subinhibitory concentrationsof antibiotics to alter K. pneumoniae capsule polysaccharide (CPS) production and survival innormal human serum. Several antibiotics tested enhanced ST258 survival in normal humanserum. Unexpectedly, subinhibitory concentrations of mupirocin increased survival in 7 of 10clinical isolates tested, and caused up-regulated expression of CPS biosynthesis genes and CPSproduction in a selected ST258 clinical isolate (34446) compared with untreated controls.Additionally, mupirocin treatment caused a reduction in the deposition of the serum complementproteins C3b and C5b-9 on the surface of ST258. Transcriptome analyses with isolate 34446indicated that genes implicated in serum resistance, such as aroE, csrD, pyrB, pyrC and traT,were up-regulated following mupirocin treatment. In conclusion, mupirocin causes changes inthe K. pneumoniae transcriptome that likely contribute to the observed decrease in serumsusceptibility via a multifactorial process. Whether these responses are triggered by othercomponents of host defense or therapeutics that were not tested here merits further investigation.
2022-10-12 | GSE201383 | GEO