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Tracking clonal and plasmid transmissions in colistin- and carbapenem-resistant Klebsiella pneumoniae

ABSTRACT: Tracking clonal and plasmid transmissions in Col-CRKpn

PROVIDER: PRJEB76496 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	ERR13253000_1.fastq.gz	Fastqsanger.gz
	ERR13253000_2.fastq.gz	Fastqsanger.gz
	ERR13253001_1.fastq.gz	Fastqsanger.gz
	ERR13253001_2.fastq.gz	Fastqsanger.gz

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Clonal Dissemination of Plasmid-Mediated Carbapenem and Colistin Resistance in Refugees Living in Overcrowded Camps in North Lebanon.

Project description:Carbapenem and colistin-resistant bacteria represent a global public health problem. Refugees carrying these bacteria and living in inadequate shelters can spread these microorganisms. The aim of this study was to investigate the intestinal carriage of these bacteria in Syrian refugees in Lebanon. Between June and July 2019, 250 rectal swabs were collected from two refugee camps in North Lebanon. Swabs were cultured on different selective media. Antibiotic susceptibility testing was performed using the disk diffusion method. Carbapenemase-encoding genes and mcr genes were investigated using real-time polymerase chain reaction (RT-PCR) and standard polymerase chain reaction (PCR). Epidemiological relatedness was studied using multilocus sequence typing (MLST). From 250 rectal swabs, 16 carbapenem-resistant, 5 colistin-resistant, and 4 colistin and carbapenem-resistant Enterobacteriaceae were isolated. The isolates exhibited multidrug-resistant phenotypes. Seven Klebsiella pneumoniae isolates harboured the blaOXA-48 gene, and in addition four K. pneumoniae had mutations in the two component systems pmrA/pmrB, phoP/phoQ and co-harboured the blaNDM-1 gene. Moreover, the blaNDM-1 gene was detected in six Escherichia coli and three Enterobacter cloacae isolates. The remaining five E. coli isolates harboured the mcr-1 gene. MLST results showed several sequence types, with a remarkable clonal dissemination. An urgent strategy needs to be adopted in order to avoid the spread of such resistance in highly crowded underserved communities.

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Clonal Tracking Uncovers Barriers and Validate New Strategies to Enhance Gene Editing in Human Hematopoietic Stem Cells [BAR-seq]

Project description:By applying a barcoding strategy to clonal tracking of edited cells (BAR-seq), we show that p53 activation triggered by HDR editing significantly shrink the HSPC clonal repertoire in hematochimeric mice, despite engrafted edited clones preserved multilineage and self-renewing capacity. Transient inhibition of p53 restored polyclonal graft composition. We then overcame HSC constraints to HDR by forcing cell cycle progression and upregulating components of the HDR machinery through transient expression of Adenovirus 5 E4orf6/7 protein, which operates the major cell cycle controller E2F. Combined E4orf6/7 expression and p53 inhibition resulted in high and stable HDR editing efficiencies in the human graft, without perturbing repopulation and self-renewing properties of edited HSCs.

2020-04-22 | GSE144340 | GEO

Clonal Tracking Uncovers Barriers and Validate New Strategies to Enhance Gene Editing in Human Hematopoietic Stem Cells [RNA-seq]

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Genetic tracking of Vibrio cholerae

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Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA.

Project description:Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

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Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation

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Global protein responses of multi-drug resistant plasmid containing Escherichia coli to beta-lactams and ciprofloxacin.

Project description:Our study aimed to analyse the responses of the clonal ST131 strain, containing the ESBL and multi-drug resistance plasmid under different beta-lactam and ciprofloxacin antibiotic stress in comparison with no antibiotic stresses in order to identify the specific response of a MDR plasmid to the specific antibiotic and the potential interaction between the plasmid and the host bacteria under different stresses. The aim was to understand how the plasmid and bacterial host proteins are influenced by the different antibiotic stresses. By analysing these factors systematically we aimed to identify the pathways and core or antibiotic specific responses of the bacteria. Using proteomics we provide an unbiased protein map of a pathogen with a MDR plasmid under antibiotic stress and compare it with the same bacteria in the absence of the stress.

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High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance

Project description:It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400.000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analysed. Fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference within tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. The ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype was found at a frequency of 0.6-3.3%. With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for evaluating the contribution of stochastic and deterministic clonal selection processes in response to IR.

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In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis

Project description:In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis

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Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

Project description:BackgroundExisting surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown.MethodsA retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100,000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay.ResultsFrom 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100,000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria.ConclusionsColistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home.

| S-EPMC4296128 | biostudies-literature

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