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Klebsiella pneumoniae subsp. pneumoniae ST258

ABSTRACT: Molecular dissection of the evolution of carbapenem-resistant ST258 Klebsiella pneumoniae

PROVIDER: PRJNA237670 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1166950_1.fastq.gz	Fastqsanger.gz
	SRR1166950_2.fastq.gz	Fastqsanger.gz
	SRR1166960_1.fastq.gz	Fastqsanger.gz
	SRR1166960_2.fastq.gz	Fastqsanger.gz
	SRR1166970_1.fastq.gz	Fastqsanger.gz

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Vaccine protection against multidrug-resistant Klebsiella pneumoniae in a non-human primate model of severe lower respiratory tract infection

Project description:Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance-a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and can be resistant to many classes of clinically useful antibiotics. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiograph 24 h after intrabronchial installation of 108 CFUs of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support to the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this approach can be extended to include multiple capsule types

2019-11-26 | GSE137135 | GEO

Subinhibitory Concentrations of Antibiotics Alter the Response of Klebsiella pneumoniae to Components of Innate Host Defense

Project description:Carbapenem-resistant Klebsiella pneumoniae classified as multilocus sequence type 258 (ST258)are a problem in healthcare settings in many countries globally. ST258 isolates are resistant tomultiple classes of antibiotics and can cause life-threatening infections, such as pneumonia andsepsis, in susceptible individuals. Treatment strategies for such infections are limited. Hence,understanding the response of K. pneumoniae to host factors in the presence of antibiotics couldreveal mechanisms employed by the pathogen to evade killing in the susceptible host, as well asinform treatment of infections. Here, we investigated the ability of subinhibitory concentrationsof antibiotics to alter K. pneumoniae capsule polysaccharide (CPS) production and survival innormal human serum. Several antibiotics tested enhanced ST258 survival in normal humanserum. Unexpectedly, subinhibitory concentrations of mupirocin increased survival in 7 of 10clinical isolates tested, and caused up-regulated expression of CPS biosynthesis genes and CPSproduction in a selected ST258 clinical isolate (34446) compared with untreated controls.Additionally, mupirocin treatment caused a reduction in the deposition of the serum complementproteins C3b and C5b-9 on the surface of ST258. Transcriptome analyses with isolate 34446indicated that genes implicated in serum resistance, such as aroE, csrD, pyrB, pyrC and traT,were up-regulated following mupirocin treatment. In conclusion, mupirocin causes changes inthe K. pneumoniae transcriptome that likely contribute to the observed decrease in serumsusceptibility via a multifactorial process. Whether these responses are triggered by othercomponents of host defense or therapeutics that were not tested here merits further investigation.

2022-10-12 | GSE201383 | GEO

Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae

Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.

2024-10-01 | GSE272297 | GEO

Klebsiella pneumoniae subsp. pneumoniae ST258-K28BO

Project description:Klebsiella pneumoniae ST258-K28BO Genome Sequencing

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Klebsiella pneumoniae subsp. pneumoniae ST258-K26BO

Project description:Klebsiella pneumoniae ST258-K26BO Genome Sequencing

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An Acquired Acyltransferase Promotes Klebsiella pneumoniae ST258 Respiratory Infection

Project description:Klebsiella pneumoniae ST258 are human pathogens associated with poor outcomes in patients worldwide. We identified a member of the acyltransferase superfamily 3 (atf3), enriched within the ST258 clade, that provides a major competitive advantage for the proliferation of this group of organisms in vivo. Comparison of a wild type ST258 strain (KP35) and a atf3 isogenic mutant generated by Crispr-Cas9 targeting, revealed increased NADH:quinone oxidoreductase transcription and ATP generation, fueled by increased glycolysis. Acquisition of atf3 induced changes in the bacterial acetylome, promoting lysine acetylation of multiple gene products involved in central metabolism, specifically Zwf (glucose-6 phosphate dehydrogenase). The atf3-mediated metabolic boost led to greater consumption of glucose in the host airway and increased bacterial burden in the lung, independent of cytokine levels and immune cell recruitment. Acquisition of a promiscuous acyltransferase enhances K. pneumoniae ST258 fitness and promotes its emergence as a major health care associated pathogen.

2021-04-12 | MSV000087181 | MassIVE

Synergistic effects of polymyxin and vancomycin combinations on carbapenem- and polymyxin-resistant Klebsiella pneumoniae and their molecular characteristics

Project description:The emergence and spread of polymyxin resistance, especially among Klebsiella pneumoniae isolates threaten the effective management of infections. This study profiled for polymyxin resistance mechanisms and investigated the activity of polymyxins plus vancomycin against carbapenem- and polymyxin-resistant K. pneumoniae.

2023-10-13 | PXD045685 | JPOST Repository

Klebsiella pneumoniae strain:ST258

Project description:Klebsiella pneumoniae strain:ST258 Genome sequencing and assembly

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Proteomic analysis of carbapenem-resistant Klebsiella pneumoniae exposure to tigecycline and aminoglycosides

Project description:Proteomic analysis of carbapenem-resistant Klebsiella pneumoniae exposure to tigecycline and aminoglycosides

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Whole transcriptomic analysis of mechanisms of tolerance and resistance to chlorhexidine in carbapenemase-producing Klebsiella pneumoniae clinical strains

Project description:The increasing resistence and/or bacterial tolerance to bactericides, such as chlorhexidine, causes worrisome public health problems. Using transcriptomical and microbiological studies, we analysed the molecular mechanisms associated with the adaptation to chlorhexidine in two carbapenemase-producing strains of Klebsiella pneumoniae belonging ST258-KPC3 and ST846-OXA48.

2020-03-21 | GSE147316 | GEO

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