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Acinetobacter baumannii

ABSTRACT: MDRO-SNAP: MultiDrug Resistant Organism Network - Study Network of Acinetobacter baumannii as Carbapenem-Resistant Pathogen (SNAP)

PROVIDER: PRJNA906166 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22455200_1.fastq.gz	Fastqsanger.gz
	SRR22455200_2.fastq.gz	Fastqsanger.gz
	SRR22455300_1.fastq.gz	Fastqsanger.gz
	SRR22455300_2.fastq.gz	Fastqsanger.gz
	SRR22455400_1.fastq.gz	Fastqsanger.gz

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Deep learning-guided discovery of a narrow-spectrum antibiotic against Acinetobacter baumannii

Project description:Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug-resistance due to its robust outer membrane and its ability to acquire and retain extracellular DNA. Moreover, it can survive for prolonged durations on surfaces and is resistant to desiccation. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new chemical matter with antibacterial activity against this burdensome pathogen. Here, we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a deep neural network with this growth inhibition dataset and performed predictions on the Drug Repurposing Hub for structurally novel molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii, which could overcome intrinsic and acquired resistance mechanisms in clinical isolates. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE, a functionally conserved protein that contributes to shuttling lipoproteins from the inner membrane to the outer membrane. Moreover, abaucin was able to control an A. baumannii infection in a murine wound model. Together, this work highlights the utility of machine learning in discovering new antibiotics and describes a promising lead with narrow-spectrum activity against a challenging Gram-negative pathogen.

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The transcriptomic response of Acinetobacter baumannii to colistin and doripenem alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model

Project description:Objectives: Colistin remains a last-line treatment for multidrug-resistant Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against multidrug-resistant strains. In order to understand the bacterial responses to these antibiotics we analysed the transcriptome of A. baumannii following exposure to each.

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Transcription profiling of Acinetobacter baumannii multi-drug resistant strain and a susceptible reference strain - Abefflux

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Pseudomonas aeruginosa

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Outer membrane vesicles of clinical tet(x3), blaNDM-1, and blaOXA-97-carrying Acinetobacter baumannii isolates contribute to carbapenem resistance

Project description:Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAb) are associated with high patient morbidity and mortality. The serious threat for human health imposed by CRAb was recently underscored by identification of close-to-untouchable carbapenem- and tetracycline-resistant isolates. Since outer membrane vesicles (OMVs) of Gram-negative bacteria may contribute to antimicrobial resistance, our present study was aimed at investigating OMVs produced by the first two carbapenem- and tetracycline-resistant CRAb isolates in Europe. These isolates, denoted CRAb1 and CRAb2 contain large, nearly identical plasmids that specify multiple resistances. Both isolates produce OMVs that were analyzed by differential light scattering, transmission electron microscopy and proteomics. By comparison with OMVs from the plasmid-free non-carbapenem-resistant A. baumannii isolate Ab1, which is an isogenic ancestor of the CRAb1 isolate, we show that plasmid carriage by the CRAb1 and CRAb2 isolates leads to an increased OMV size that is accompanied by increased diversity of the OMV proteome. Our analyses show that OMVs from CRAb1 and CRAb2 are major reservoirs of proteins involved in antimicrobial resistance, including the plasmid-encoded carbapenemases BlaNDM-1, and BlaOXA-97. We also show that these OMV-borne carbapenemases hydrolyze imipenem and protect otherwise carbapenem-sensitive A. baumannii and Escherichia coli isolates against this antibiotic. Altogether, our observations show that OMVs from highly drug-resistant CRAb confer tolerance against last-resort antibiotics to non-resistant bacterial pathogens.

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Project description:Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen (SNAP)

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