Project description:This SuperSeries is composed of the following subset Series: GSE35746: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [tiling arrays] GSE35821: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [TSS-Seq] Refer to individual Series
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.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain AJ218.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain KPC2.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to Klebsiella pneumoniae complex strains AJ055, AJ218, AJ292, KPC2, 03-311-0071 and 04153260899A.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, 5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. This submission contains the results from six Klebsiella strains (four Klebsiella variicola: AJ005, AJ292, 03-311-0071, 04153260899A and two Klebsiella pneumoniae: AJ218, KPC2) grown in either RPMI or pooled human sera. Six replicates of each condition were subjected to shotgun proteomics and label-free MS1-based quantitation.
Project description:Recently, we have reported on a highly drug-resistant carbapenemase-producing isolate of Enterobacter cloacae (Nepal et al., Virulence. 2018; 9: 1377-1389). In the present study, we asked the question whether and, if so, how this isolate responds to a sub-inhibitory challenge with the antibiotic imipenem. To answer this question, we applied a SILAC proteomics approach that allowed the quantification of changes in the relative abundance of bacterial protein in response to imipenem. The results show that the investigated E. cloacae isolate mounts a highly specific response to counteract the detrimental effects of imipenem.