Acinetobacter, Klebsiella, Pseudomonas, Enterobacter
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA411997 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR8618098_1.fastq.gz | Fastqsanger.gz | |||
| SRR8618098_2.fastq.gz | Fastqsanger.gz | |||
| SRR8618099_1.fastq.gz | Fastqsanger.gz | |||
| SRR8618099_2.fastq.gz | Fastqsanger.gz |
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Project description:Acinetobacter baumannii is an ESKAPE pathogen that rapidly develops resistance to antibiotics and persists for extended periods in the host or on abiotic surfaces. Survival in environmental stress such as phosphate scarcity, represents a clinically significant challenge for nosocomial pathogens. In the face of phosphate starvation, certain bacteria encode adaptive strategies, including the substitution of glycerophospholipids with phosphorus-free lipids. In bacteria, phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin are conserved glycerophospholipids that form lipid bilayers. Here, we demonstrate that in response to phosphate limitation, conserved regulatory mechanisms induce aminolipid production in A. baumannii. Specifically, phosphate limitation induces formation of three lipids, including amine-containing ornithine and lysine aminolipids. We show that phospahte limitation induced transcription of the olsB gene. Mutations that inactivate aminolipid biosynthesis exhibit fitness defects relative to wild type in colistin growth and killing assays.
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Project description:Acinetobacter baumannii is a Gram-negative ESKAPE pathogen, accountable for lethal nosocomial infections, owing to its high pathogenicity and multi-drug resistance (MDR). Hence, the World Health Organization (WHO) has prioritized this bacterium against which new pharmacophores are required urgently. Therefore, this study evaluates the antimicrobial potential of lithium complex based on salicylic acid, and 1,10-phenanthroline ([Li(phen)2sal]) against MDR A. baumannii (MDRAB) through growth inhibition, time-kill assay, biofilm inhibition, and eradication alongside microscopy. The mechanism of action was proposed by flow cytometry and proteomic analysis. Moreover, its in-vivo efficacy was assessed using A. baumannii-induced pneumonia model in mice. Results showed that lithium complex significantly inhibited the bacterial growth at 16-32 µg/ml. Time kill analysis revealed that the compound retarded the bacterial growth after 2-3 h of treatment. Lithium complex significantly inhibited and eradicated >70% of biofilms at the MIC level which is a key problem of indwelling and prosthetic devices. Light and atomic force microscopy further indicated disarticulated biofilm and ruptured cellular membrane post-lithium complex treatment. Proteomic analysis revealed that lithium complex exerted oxidative stress on A. baumannii which may contribute to cell rupturing. Flow cytometry confirmed the role of lithium complex in cytoplasmic membrane disintegration. The compound ameliorated the pneumonia symptoms at non-toxic doses of 20 and 40 mg/kg in the pre-clinical A. baumannii-induced pneumonia model as evident by the significant reduction in bacterial burden and parenchymal inflammation. Taken together, these findings suggest that the lithium complex can be a potential drug candidate against MDR A. baumannii.
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Project description:BackgroundPersonalized body-worn alcohol dispensers may serve as an important tool for perioperative infection control, but the impact of these devices on the epidemiology of transmission of high-risk Enterococcus , Staphylococcus aureus , Klebsiella, Acinetobacter , Pseudomonas , and Enterobacter (ESKAPE) pathogens is unknown. We aimed to characterize the epidemiology of ESKAPE transmission in the pediatric anesthesia work area environment with and without a personalized body-worn alcohol dispenser.MethodsThis controlled before and after study included 40 pediatric patients enrolled over a 1-year study period. Two groups of operating room cases were compared: (1) operating room cases caring for patients with usual care (December 17, 2019, to August 25, 2020), and (2) operating room cases caring for patients with usual care plus the addition of a personalized, body-worn alcohol hand rub dispenser (September 30, 2020, to December 16, 2020). Operating rooms were randomly selected for observation of ESKAPE transmission in both groups. Device use was tracked via wireless technology and recorded in hourly hand decontamination events.ResultsAnesthesia providers used the alcohol dispenser 3.3 ± 2.1 times per hour. A total of 57 ESKAPE transmission events (29 treatment and 28 control) were identified. The personalized body-worn alcohol dispenser impacted ESKAPE transmission by increasing the contribution of provider hand contamination at case start (21/29 device versus 10/28 usual care; relative risk, [RR] 2.03; 99.17% confidence interval [CI], 1.025-5.27; P = .0066) and decreasing the contribution of environmental contamination at case end (3/29 device versus 12/28 usual care; RR, 0.24; 99.17% CI, 0.022-0.947; P = .0059). ESKAPE pathogen contamination involved 20% (8/40) of patient intravascular devices. There were 85% (34/40) of preoperative patient skin surfaces contaminated with ≥1 (1.78 ± 0.19 [standard deviation {SD}]) ESKAPE pathogens.ConclusionsA personalized body-worn alcohol dispenser can impact the epidemiology of ESKAPE transmission in the pediatric anesthesia work area environment. Improved preoperative patient decolonization and vascular care are indicated to address ESKAPE pathogens among pediatric anesthesia work area reservoirs.
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Project description:The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor LOX-1. OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotic.
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