scholarly journals Animal Model To Study Klebsiella pneumoniae Gastrointestinal Colonization and Host-to-Host Transmission

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Gi Tract ◽  
Content Type ◽  
Immunocompetent Mice

ABSTRACT An important yet poorly understood facet of the life cycle of a successful pathogen is host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae, a Gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat, as K. pneumoniae has become multidrug resistant. Epidemiological studies suggest that K. pneumoniae host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Here, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of K. pneumoniae through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we showed that K. pneumoniae can asymptomatically colonize the GI tract in immunocompetent mice and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent K. pneumoniae isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, K. pneumoniae carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient supershedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors toward K. pneumoniae dissemination.

scholarly journals An Animal Model to Study Klebsiella pneumoniae Gastro-Intestinal Colonization and Host-to-Host Transmission

2020 ◽  
Author(s):  
Taylor M. Young ◽  
Andrew S. Bray ◽  
Ravinder K. Nagpal ◽  
David L. Caudell ◽  
Hariom Yadav ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Close Contact ◽  
Epidemiological Studies ◽  
Transmission Efficiency ◽  
Oral Route ◽  
Human Infection ◽  
Drug Resistant ◽  
Gi Tract ◽  
Fecal Shedding ◽  
Immunocompetent Mice

AbstractAn important yet poorly understood facet in the life cycle of a successful pathogen is the host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae (Kpn), a gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat as Kpn has become multi-drug resistant. Epidemiological studies suggest that Kpn host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Herein, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of Kpn through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we show that Kpn can asymptomatically colonize the GI tract of immunocompetent mice, and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent Kpn isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, Kpn carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient super-shedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors towards Kpn dissemination.

scholarly journals Emergence of Epidemic Multidrug-Resistant Enterococcus faecium from Animal and Commensal Strains

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
François Lebreton ◽  
Willem van Schaik ◽  
Abigail Manson McGuire ◽  
Paul Godfrey ◽  
Allison Griggs ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Sequence Data ◽  
Mobile Element ◽  
Multidrug Resistant ◽  
Human Infection ◽  
Animal Origin ◽  
Loss Of Function ◽  
Content Type ◽  
Hospital Acquired Infection ◽  
Hospital Acquired

ABSTRACTEnterococcus faecium, natively a gut commensal organism, emerged as a leading cause of multidrug-resistant hospital-acquired infection in the 1980s. As the living record of its adaptation to changes in habitat, we sequenced the genomes of 51 strains, isolated from various ecological environments, to understand howE. faeciumemerged as a leading hospital pathogen. Because of the scale and diversity of the sampled strains, we were able to resolve the lineage responsible for epidemic, multidrug-resistant human infection from other strains and to measure the evolutionary distances between groups. We found that the epidemic hospital-adapted lineage is rapidly evolving and emerged approximately 75 years ago, concomitant with the introduction of antibiotics, from a population that included the majority of animal strains, and not from human commensal lines. We further found that the lineage that included most strains of animal origin diverged from the main human commensal line approximately 3,000 years ago, a time that corresponds to increasing urbanization of humans, development of hygienic practices, and domestication of animals, which we speculate contributed to their ecological separation. Each bifurcation was accompanied by the acquisition of new metabolic capabilities and colonization traits on mobile elements and the loss of function and genome remodeling associated with mobile element insertion and movement. As a result, diversity within the species, in terms of sequence divergence as well as gene content, spans a range usually associated with speciation.IMPORTANCEEnterococci, in particular vancomycin-resistantEnterococcus faecium, recently emerged as a leading cause of hospital-acquired infection worldwide. In this study, we examined genome sequence data to understand the bacterial adaptations that accompanied this transformation from microbes that existed for eons as members of host microbiota. We observed changes in the genomes that paralleled changes in human behavior. An initial bifurcation within the species appears to have occurred at a time that corresponds to the urbanization of humans and domestication of animals, and a more recent bifurcation parallels the introduction of antibiotics in medicine and agriculture. In response to the opportunity to fill niches associated with changes in human activity, a rapidly evolving lineage emerged, a lineage responsible for the vast majority of multidrug-resistantE. faeciuminfections.

scholarly journals Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones

2021 ◽  
Author(s):  
Mattia Palmieri ◽  
Kelly L. Wyres ◽  
Caroline Mirande ◽  
Zhao Qiang ◽  
Ye Liyan ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Content Type ◽  
Origin And Evolution ◽  
Link Type ◽  
Beijing China

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

scholarly journals Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains

2020 ◽  
Vol 6 (12) ◽  
Author(s):  
Katlego Kopotsa ◽  
Nontombi M. Mbelle ◽  
John Osei Sekyere
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Type I ◽  
Bacteriophage Therapy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Plasmid Replicon ◽  
Size Number ◽  
Plasmid Size ◽  
Epidemiological Trends

Carbapenem-resistant Klebsiella pneumoniae (CRKP) remains a major clinical pathogen and public health threat with few therapeutic options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping by repetitive element palindromic (REP)-PCR, plasmid size, number, incompatibility and mobility analyses, and PacBio’s SMRT sequencing (n=6). There were 56 multidrug-resistant CRKP, having bla OXA-48-like and bla NDM-1/7 carbapenemases on self-transmissible IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon was present in 56 strains. Whole-genome sequencing of six strains revealed least 41 virulence genes, extensive ompK36 mutations, and four different K- and O-loci types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring m6A (G A TC, G A TGNNNNNNTTG, CA A NNNNNNCATC motifs) and m4C (C C WGG) modifications on chromosomes and plasmids, were found. The nature of plasmid-mediated, clonal and multi-clonal dissemination of blaOXA-48-like and blaNDM-1 mirrors epidemiological trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both bla OXA-48 and bla NDM-1 in the same isolates was observed. Plasmid-mediated transmission of RMS, virulome and prophages influence bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on antimicrobial and bacteriophage therapy needs urgent investigation.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Phage Sweeny

2019 ◽  
Vol 8 (39) ◽  
Author(s):  
Nicholas Martinez ◽  
Eric Williams ◽  
Heather Newkirk ◽  
Mei Liu ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Complete Genome Sequence ◽  
Protein Level ◽  
Multidrug Resistant ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Multidrug Resistant Bacterium ◽  
Protein Encoding ◽  
Hospital Acquired ◽  
Encoding Genes

Klebsiella pneumoniae is a multidrug-resistant bacterium causing many severe hospital-acquired infections. Here, we describe siphophage Sweeny that infects K. pneumoniae. Of its 78 predicted protein-encoding genes, a functional assignment was given to 36 of them. Sweeny is most closely related to T1-like phages at the protein level.

scholarly journals Elucidating the Regulon of Multidrug Resistance Regulator RarA in Klebsiella pneumoniae

2013 ◽  
Vol 57 (4) ◽  
pp. 1603-1609 ◽  
Author(s):  
Shyamasree De Majumdar ◽  
Mark Veleba ◽  
Sarah Finn ◽  
Séamus Fanning ◽  
Thamarai Schneiders
Keyword(s):  
Klebsiella Pneumoniae ◽  
Cell Envelope ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Protein Synthesis Inhibitors ◽  
Content Type ◽  
Phenotypic Microarray ◽  
Genes Encoding ◽  
Clusters Of Orthologous Groups ◽  
Microarray Analyses

ABSTRACTRarA is an AraC-type regulator inKlebsiella pneumoniae, which, when overexpressed, confers a low-level multidrug-resistant (MDR) phenotype linked to the upregulation of both theacrABandoqxABefflux genes. IncreasedrarAexpression has also been shown to be integral in the development of tigecycline resistance in the absence oframAinK. pneumoniae. Given its phenotypic role in MDR, microarray analyses were performed to determine the RarA regulon. Transcriptome analysis was undertaken using strains Ecl8ΔrarA/pACrarA-2 (rarA-expressing construct) and Ecl8ΔrarA/pACYC184 (vector-only control) using bespoke microarray slides consisting of probes derived from the genomic sequences ofK. pneumoniaeMGH 78578 (NC_009648.1) and Kp342 (NC_011283.1). Our results show thatrarAoverexpression resulted in the differential expression of 66 genes (42 upregulated and 24 downregulated). Under the COG (clusters of orthologous groups) functional classification, the majority of affected genes belonged to the category of cell envelope biogenesis and posttranslational modification, along with genes encoding the previously uncharacterized transport proteins (e.g., KPN_03141,sdaCB, andleuE) and the porin OmpF. However, genes associated with energy production and conversion and amino acid transport/metabolism (e.g.,nuoA,narJ, andproWX) were found to be downregulated. Biolog phenotype analyses demonstrated thatrarAoverexpression confers enhanced growth of the overexpresser in the presence of several antibiotic classes (i.e., beta-lactams and fluoroquinolones), the antifungal/antiprotozoal compound clioquinol, disinfectants (8-hydroxyquinoline), protein synthesis inhibitors (i.e., minocycline and puromycin), membrane biogenesis agents (polymyxin B and amitriptyline), DNA synthesis (furaltadone), and the cytokinesis inhibitor (sanguinarine). Both our transcriptome and phenotypic microarray data support and extend the role of RarA in the MDR phenotype ofK. pneumoniae.

scholarly journals Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Approaches ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surface Polysaccharides ◽  
Resistant Strains ◽  
Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Strain TK421, a Conjugative Hypervirulent Isolate

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Travis J. Kochan ◽  
Egon A. Ozer ◽  
Nathan B. Pincus ◽  
Margaret A. Fitzpatrick ◽  
Alan R. Hauser
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Nosocomial Infections ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Multidrug Resistant ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Content Type ◽  
Rapid Dissemination

Klebsiella pneumoniae is a Gram-negative bacterium that is a major cause of nosocomial infections worldwide. Here, we present the complete genome sequence of TK421, a clinical bacteremia isolate containing a hypervirulence plasmid carrying tra-associated conjugation machinery genes. Emergence of conjugative hypervirulence plasmids could portend rapid dissemination of hypervirulence among multidrug-resistant K. pneumoniae strains.

scholarly journals Complete Genome Sequence of Klebsiella pneumoniae Myophage May

2019 ◽  
Vol 8 (19) ◽  
Author(s):  
Katherine T. Nguyen ◽  
Rachele Bonasera ◽  
Garret Benson ◽  
Adriana C. Hernandez-Morales ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Resistant Strains

May is a newly isolated myophage that infects multidrug-resistant strains of Klebsiella pneumoniae, a pathogen that is associated with antibiotic-resistant infections in humans. The genome of May has been shown to be similar to that of phage Vi01.

scholarly journals Evidence of Sharing ofKlebsiella pneumoniaeStrains between Healthy Companion Animals and Cohabiting Humans

2019 ◽  
Vol 57 (6) ◽  
Author(s):  
Cátia Marques ◽  
Adriana Belas ◽  
Catarina Aboim ◽  
Patrícia Cavaco-Silva ◽  
Graça Trigueiro ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Close Contact ◽  
Companion Animals ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Content Type ◽  
Healthy Humans ◽  
Tract Infections ◽  
Healthy Participants

ABSTRACTThis study aimed to characterize the fecal colonization and sharing ofKlebsiella pneumoniaestrains between companion animals and humans living in close contact. Fecal samples were collected from 50 healthy participants (24 humans, 18 dogs, and 8 cats) belonging to 18 households. Samples were plated onto MacConkey agar (MCK) plates with and without cefotaxime or meropenem supplementation. Up to fiveK. pneumoniaecolonies per participant were compared by pulsed-field gel electrophoresis (PFGE) after XbaI restriction.K. pneumoniaestrains with unique pulse types from each participant were characterized for antimicrobial susceptibility, virulence genes, and multilocus sequence type (MLST). FecalK. pneumoniaepulse types were compared to those of clinicalK. pneumoniaestrains from animal and human patients with urinary tract infections (n = 104).K. pneumoniaecolonization was detected in nonsupplemented MCK in around 38% of dogs (n = 7) and humans (n = 9).K. pneumoniaestrains isolated from dogs belonged to sequence type 17 (ST17), ST188, ST252, ST281, ST423, ST1093, ST1241, ST3398, and ST3399. None of theK. pneumoniaestrains were multidrug resistant or hypervirulent. Two households included multiple colonized participants. Notably, two colonized dogs within household 15 (H15) shared a strain each (ST252 and ST1241) with one coliving human. One dog from H16 shared one PFGE-undistinguishableK. pneumoniaeST17 strain with two humans from different households; however, the antimicrobial susceptibility phenotypes of these three strains differed. Two main virulence genotypes were detected, namelyfimH-1 mrkD ycfM entB kfuandfimH-1 mrkD ycfM entB kpn. These results highlight the potential role of dogs as a reservoir ofK. pneumoniaeto humans and vice versa. Furthermore, to our best knowledge, this is the first report of healthy humans and dogs sharingK. pneumoniaestrains that were undistinguishable by PFGE/MLST.

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