Outbreak of E. cloacae
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB46126 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6415300_1.fastq.gz | Fastqsanger.gz | |||
| ERR6415300_2.fastq.gz | Fastqsanger.gz | |||
| ERR6415310_1.fastq.gz | Fastqsanger.gz | |||
| ERR6415310_2.fastq.gz | Fastqsanger.gz | |||
| ERR6415320_1.fastq.gz | Fastqsanger.gz |
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Project description:The spread of antimicrobial resistance (AMR), coupled with the decline in antibiotic development, has become a major public health concern. Recent studies estimate that around 700,000 people die each year from infections caused by multidrug-resistant (MDR) bacteria. This led the WHO to publish the ESKAPEE list of high priority pathogens for AMR, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli. Among these, Gram-negative bacteria (K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and E. coli) are particularly overrepresented. This is mainly due to their high propensity to develop multiple resistance mechanisms, in addition to their intrinsic resistance to many antimicrobials, which is due to their membrane composition and the expression of broad-spectrum efflux pumps. One strategy to combat such AMR is the use of drug enhancers that are able to restore the antibacterial activity of poorly active antibiotics. In this context, we demonstrated that the polyamino-isoprenyl enhancer, NV716, efficiently potentiates the antibacterial activity of two families of multi-target Ser/Cys-based enzyme inhibitors, namely the oxadiazolone derivatives (OX) and the Cyclipostins and Cyclophostin analogs (CyC), against Enterobacter cloacae, while remaining inactive against other Gram-negative bacteria. We confirmed that NV716 potentiates some OX & CyC compounds by permeabilizing the outer membrane and thus by increasing the inhibitor accumulation as shown by fluorescence confocal microscopy. By using bio-orthogonal click-chemistry activity-based protein profiling (CC-ABPP) approach coupled to proteomic analysis, we also identified the target proteins of the best OX & CyC inhibitors from E. cloacae lysate, thereby confirming their multi-target nature. Interestingly, 6 of the latter proteins were also captured via CC-ABPP in P. aeruginosa lysate, and are highly conserved in all Gram-negative bacteria. These results provide proof of concept that both OX & CyC, if successfully potentiated, could be used against a wide range of ESKAPEE Gram-negative bacteria.
2025-02-27 | PXD053955 | Pride
Project description:Elucidating the RamA Regulon in Klebsiella pneumoniae and the transcriptome profiles of multidrug resistant Klebsiella pneumoniae
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Project description:Multidrug-resistant tuberculosis outbreak in LAN gaming centers, Singapore
| PRJEB6717 | ENA
Project description:The spread of antimicrobial resistance (AMR), coupled with the decline in antibiotic development, has become a major public health concern. Recent studies estimate that around 700,000 people die each year from infections caused by multidrug-resistant (MDR) bacteria. This led the WHO to publish the ESKAPEE list of high priority pathogens for AMR, namely Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli. Among these, Gram-negative bacteria (K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and E. coli) are particularly overrepresented. This is mainly due to their high propensity to develop multiple resistance mechanisms, in addition to their intrinsic resistance to many antimicrobials, which is due to their membrane composition and the expression of broad-spectrum efflux pumps. One strategy to combat such AMR is the use of drug enhancers that are able to restore the antibacterial activity of poorly active antibiotics. In this context, we demonstrated that the polyamino-isoprenyl enhancer, NV716, efficiently potentiates the antibacterial activity of two families of multi-target Ser/Cys-based enzyme inhibitors, namely the oxadiazolone derivatives (OX) and the Cyclipostins and Cyclophostin analogs (CyC), against Enterobacter cloacae, while remaining inactive against other Gram-negative bacteria. We confirmed that NV716 potentiates some OX & CyC compounds by permeabilizing the outer membrane and thus by increasing the inhibitor accumulation as shown by fluorescence confocal microscopy. By using bio-orthogonal click-chemistry activity-based protein profiling (CC-ABPP) approach coupled to proteomic analysis, we also identified the target proteins of the best OX & CyC inhibitors from E. cloacae lysate, thereby confirming their multi-target nature. Interestingly, 6 of the latter proteins were also captured via CC-ABPP in P. aeruginosa lysate, and are highly conserved in all Gram-negative bacteria. These results provide proof of concept that both OX & CyC, if successfully potentiated, could be used against a wide range of ESKAPEE Gram-negative bacteria.
2025-02-27 | PXD052024 | Pride
Project description:The upsurge of multidrug-resistant infections has rendered tuberculosis the principal cause of death among infectious diseases. A clonal outbreak multidrug-resistant triggering strain of Mycobacterium tuberculosis was identified in Kanchanaburi Province, designated “MKR superspreader”, which was found to subsequently spread to other regions, as revealed by prior epidemiological reports in Thailand. Herein, we showed that the MKR displayed a higher growth rate upon infection into host macrophages in comparison with the H37Rv reference strain. To further elucidate the MKR’s biology, we utilised RNA-Seq and differential gene expression analyses to identify host factors involved in the intracellular viability of the MKR. A set of host genes function in the cellular response to lipid pathway was found to be uniquely up-regulated in host macrophages infected with the MKR, but not those infected with H37Rv. Within this set of genes, the IL-36 cytokines which regulate host cell cholesterol metabolism and resistance against mycobacteria attracted our interest, as our previous study revealed that the MKR elevated genes associated with cholesterol breakdown during its growth inside host macrophages. Indeed, when comparing macrophages infected with the MKR to H37Rv-infected cells, our RNA-Seq data showed that the expression ratio of IL-36RN, the negative regulator of the IL-36 pathway, to that of IL-36G was greater in macrophages infected with the MKR. Furthermore, the intracellular survival of MKR was diminished with decreased IL-36RN expression. Overall, our results indicate that IL-36RN is critical for MKR intracellular survival and could serve as a new target against this emerging multidrug-resistant M. tuberculosis strain.
2022-10-28 | GSE194017 | GEO
Project description:Assembly of a multidrug resistant Enterobacter cloacae strain MNH_G6M1U
| PRJNA914082 | ENA
Project description:Background: Efflux pumps are important cofactors for carbapenem resistance in Enterobacter cloacae. The regulatory mechanism by which asmA influences efflux pump function in this species remains unclear. This study explored the regulatory role of asmA on efflux pumps in carbapenem-resistant Enterobacter cloacae. Results: Sixteen carbapenem-resistant Enterobacter cloacae were collected. All strains carried blaNDM, 87.5% of which were blaNDM-1 and 12.5% were blaNDM-5. PAβN had weak inhibition on carbapenem resistance in ST78 and strong inhibition in ST2260. ST2260(CY-8) was still resistant to carbapenems after elimination of blaNDM and could be inhibited by PAβN. However, ST78(CY-9) lost its resistance to carbapenems. Knockout of asmA reduced the MIC of ST2260 by 16-fold. ST78 showed no such changes. Growth curves revealed impaired growth only in ST2260ΔasmA. Transcriptomics/qRT-PCR revealed no significantly altered acrAB-tolC or marA expression in either strain. Membrane proteomics detected AcrB loss specifically in ST2260ΔasmA. The loss of asmA affected a wide range of membrane proteins, especially OmpW. Molecular docking predicted that AsmA could bind to AcrB, with stronger binding energy in ST78. The buried area of the CY-8 model involved 110 contact residues, while the number of contacts of the CY-9 model increased to 144. The AsmA chain of the two models had 46 common contact residues, and the AcrB chain had 60 common contact residues. AcrB of ST78 generally carries the I277V mutation. Conclusion: asmA is highly conserved in Enterobacter cloacae. It has functional heterogeneity in different ST types. In ST2260, asmA can affect efflux pump-mediated carbapenem resistance. AsmA can regulate AcrAB-TolC not by affecting marA. It is predicted that AsmA can maintain the carbapenem resistance of Enterobacter cloacae ST2260 by helping AcrB anchor to the inner membrane. The difference in carbapenem resistance mediated by efflux pumps between ST78 and ST2260 suggests that ST78 commonly carries the AcrB I277V mutation, which is a key site for efflux of β-lactams.
2025-08-08 | GSE304310 | GEO
Project description:Hospital environment and outbreak investigation of multidrug-resistant gram-negative bacteria
| PRJEB76256 | ENA
Project description:Enterobacter cloacae is a Gram-negative nosocomial pathogen of the ESKAPE (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp.) priority group with increasing multi-drug resistance via the acquisition of resistance plasmids. However, E. cloacae can also display forms of antibiotic refractoriness, such as heteroresistance and tolerance. Here, we report that E. cloacae displays transient heteroresistance to aminoglycosides, which is accompanied with the formation of small colony variants (SCVs) with increased minimum inhibitor concentration (MIC) of gentamicin and other aminoglycosides used in the clinic, but not other antibiotic classes. To explore the underlying mechanisms, we performed RNA sequencing of heteroresistant bacteria, which revealed global gene-expression changes and a signature of the CpxRA cell envelope stress response. Deletion of the cpxRA two-component system abrogated aminoglycoside heteroresistance and SCV formation, pointing to its indispensable role in these processes. The introduction of a constitutively active allele of cpxA led to high aminoglycoside MICs, consistent with cell envelope stress response driving these behaviours in E. cloacae. Cell envelope stress can be caused by environmental cues, including heavy metals. Indeed, bacterial exposure to copper increased gentamicin MIC in the wild-type, but not in the ΔcpxRA mutant. Moreover, copper exposure also elevated the gentamicin MICs of clinical isolates from bloodstream infections, suggesting that CpxRA- and copper-dependent aminoglycoside resistance is broadly conserved in E. cloacae strains. Altogether, we establish that E. cloacae relies on transcriptional reprogramming via the envelope stress response pathway for transient resistance to a major class of frontline antibiotic.
2023-10-18 | GSE236124 | GEO