scholarly journals Gene Composition as a Potential Barrier to Large Recombinations in the Bacterial Pathogen Klebsiella pneumoniae

2019 ◽  
Vol 11 (11) ◽  
pp. 3240-3251 ◽  
Author(s):  
Francesco Comandatore ◽  
Davide Sassera ◽  
Sion C Bayliss ◽  
Erika Scaltriti ◽  
Stefano Gaiarsa ◽  
...  
Keyword(s):  
Gene Flow ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Potential Barrier ◽  
Recombination Event ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Clonal Group ◽  
Genomic Regions ◽  
Sequence Types

AbstractKlebsiella pneumoniae (Kp) is one of the most important nosocomial pathogens worldwide, able to cause multiorgan infections and hospital outbreaks. One of the most widely disseminated lineage of Kp is the clonal group 258 (CG258), which includes the highly resistant “high-risk” sequence types ST258 and ST11. Genomic investigations revealed that very large recombination events have occurred during the emergence of Kp lineages. A striking example is provided by ST258, which has undergone a recombination event that replaced over 1 Mb of the genome with DNA from an unrelated Kp donor. Although several examples of this phenomenon have been documented in Kp and other bacterial species, the significance of these very large recombination events for the emergence of either hypervirulent or resistant clones remains unclear. Here, we present an analysis of 834 Kp genomes that provides data on the frequency of these very large recombination events (defined as those involving >100 kb), their distribution within the genome, and the dynamics of gene flow within the Kp population. We note that very large recombination events occur frequently, and in multiple lineages, and that the majority of recombinational exchanges are clustered within two overlapping genomic regions, which have been involved by recombination events with different frequencies. Our results also indicate that certain lineages are more likely to act as donors to CG258. Furthermore, comparison of gene content in CG258 and non-CG258 strains agrees with this pattern, suggesting that the success of a large recombination depends on gene composition in the exchanged genomic portion.

scholarly journals Gene composition as a potential barrier to large recombinations in the bacterial pathogen Klebsiella pneumoniae

2018 ◽  
Author(s):  
Francesco Comandatore ◽  
Davide Sassera ◽  
Sion C. Bayliss ◽  
Erika Scaltriti ◽  
Stefano Gaiarsa ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Recombination Event ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Genomic Region ◽  
Gene Content ◽  
Entire Genome ◽  
Clonal Group ◽  
Recent Emergence ◽  
Genomic Regions

AbstractKlebsiella pneumoniae (Kp) is one of the most important nosocomial pathogens world-wide, being responsible for frequent hospital outbreaks and causing sepsis and multi-organ infections with a high mortality rate and frequent hospital outbreaks. The most prevalent and widely disseminated lineage of K. pneumoniae is clonal group 258 (CG258), which includes the highly resistant “high-risk” genotypes ST258 and ST11. Recent studies revealed that very large recombination events have occurred during the recent emergence of Kp lineages. A striking example is provided by ST258, which has undergone a recombination event that replaced over 1 Mb of the genome with DNA from an unrelated Kp donor. Although several examples of this phenomenon have been documented in Kp and other bacterial species, the significance of these very large recombination events for the emergence of either hyper-virulent or resistant clones remains unclear. Here we present an analysis of 834 Kp genomes that provides data on the frequency of these very large recombination events (defined as those involving >100Kb), their distribution within the genome, and the dynamics of gene flow within the Kp population. We note that very large recombination events occur frequently, and in multiple lineages, and that the majority of recombinational exchanges are clustered within two overlapping genomic regions, which result to be involved by recombination events with different frequencies. Our results also indicate that certain non-CG258 lineages are more likely to act as donors to CG258 recipients than others. Furthermore, comparison of gene content in CG258 and non-CG258 strains agrees with this pattern, suggesting that the success of a large recombination depends on gene composition in the exchanged genomic portion.Author SummaryKlebsiella pneumoniae (Kp) is an opportunistic bacterial pathogen, a major cause of deadly infections and outbreaks in hospitals worldwide. This bacterium is able to exchange large genomic portions (up to a fourth of the entire genome) within a single recombination event. Indeed, the most epidemiologically important Kp clone, is actually a hybrid which emerged after a > 1Mb recombination event. In this work, we investigated how recombinations affected the evolution of the most studied Kp Clonal Group, CG258. We found that large recombinations occurred frequently during Kp evolution, and occurred preferentially in a well-delimited genomic region. Furthermore, we found that four epidemiologically important clones emerged after large recombinations. We identified the donors of several large recombinations: despite many Kp lineages acted as donors during CG258 evolution, two of them have been involved more frequently. We hypothesize that the observed pattern of donors-recipients in recombinations, and the presence of a large recombinogenic region in Kp genome, could be related to gene composition. Indeed, genomic analyses showed a pattern compatible with this hypothesis, suggesting that gene content can represent a main factor in the success of a large recombination.

Characterization of multidrug-resistant and virulent Klebsiella pneumoniae strains belonging to the high-risk clonal group 258 (CG258) isolated from inpatients in northeastern Brazil

2021 ◽  
Author(s):  
Rafael Nakamura-Silva ◽  
Mariana Oliveira-Silva ◽  
João Pedro Rueda Furlan ◽  
Eliana Guedes Stehling ◽  
Carlos Eduardo Saraiva Miranda ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Northeastern Brazil ◽  
Clonal Group

scholarly journals Emergence of New Non–Clonal Group 258 High-Risk Clones among Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Isolates, France

2020 ◽  
Vol 26 (6) ◽  
pp. 1212-1220 ◽  
Author(s):  
Rémy A. Bonnin ◽  
Agnès B. Jousset ◽  
Adriana Chiarelli ◽  
Cécile Emeraud ◽  
Philippe Glaser ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Clonal Group ◽  
Klebsiella Pneumoniae Carbapenemase

scholarly journals Molecular epidemiology of hypervirulent Klebsiella pneumoniae: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Rahimeh Sanikhani ◽  
Mohammad Moeinirad ◽  
Fereshteh Shahcheraghi ◽  
Arezou Lari ◽  
Sepideh Fereshteh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Klebsiella Pneumoniae ◽  
Molecular Epidemiology ◽  
Liver Abscess ◽  
Molecular Typing ◽  
Web Of Science ◽  
Meta Analysis ◽  
Systemic Review ◽  
Clonal Group ◽  
Sequence Types

Classical (CKp) and hypervirulent (hvKp) Klebsiella pneumoniae are two different circulating pathotypes. The aim of this study was to assess the prevalence, epidemiology and molecular relatedness of hvKps using a systemic review and meta-analysis. The data extracted from Medline, Embase, and Web of Science and finally 14 studies met the eligible criteria. To combine prevalence proportions of all studies, we performed the metaprop command embedded in the Meta package software. Totally, of 1814 K. pneumoniae isolates, 21.7% (394/1814) were hvKp. The molecular typing showed that all hvKp isolates were grouped into 50 different sequence types (STs) of them ST23, ST11, ST65 and ST86 were common. K1, K2 and K64 were dominant capsule serotypes that strongly related to ST23, ST65 and ST11, respectively. It seems that clonal group 23 (CG23) is associated with liver abscess and CG11 related to various clinical sources.

Insights into a novel Tn4401 deletion (Tn4401i) in a multidrug-resistant Klebsiella pneumoniae clinical strain belonging to the high-risk clonal group 258 producing KPC-2

2018 ◽  
Vol 52 (4) ◽  
pp. 525-527 ◽  
Author(s):  
Bruna Fuga Araújo ◽  
Sabrina Royer ◽  
Paola Amaral Campos ◽  
Melina Lorraine Ferreira ◽  
Iara Rossi Gonçalves ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Clinical Strain ◽  
Clonal Group

scholarly journals OXA-181-Like Carbapenemases in Klebsiella pneumoniae ST14, ST15, ST23, ST48, and ST231 from Septicemic Neonates: Coexistence with NDM-5, Resistome, Transmissibility, and Genome Diversity

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Sharmi Naha ◽  
Kirsty Sands ◽  
Subhankar Mukherjee ◽  
Bijan Saha ◽  
Shanta Dutta ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Genetic Material ◽  
Neonatal Unit ◽  
New Delhi ◽  
Genome Diversity ◽  
Treatment Protocols ◽  
Middle Income ◽  
Content Type ◽  
Sequence Types

ABSTRACT Studies on the epidemiology and genomes of isolates harboring OXA-48-like genes in septicemic neonates are rare. Here, isolates producing these carbapenemases which emerged and persisted in an Indian neonatal unit were characterized in terms of their resistome, transmissibility, and genome diversity. Antibiotic susceptibility and whole-genome sequencing were carried out. The sequence types, resistome, virulome, mobile genetic elements, and transmissibility of carbapenem-resistant plasmids were evaluated. Core genome analysis of isolates was shown in a global context with other OXA-48-like carbapenemase-harboring genomes, including those from neonatal studies. Eleven OXA-48-like carbapenemase-producing Klebsiella pneumoniae (blaOXA-181, n = 7 and blaOXA-232, n = 4) isolates belonging to diverse sequence types (ST14, ST15, ST23, ST48, and ST231) were identified. blaOXA-181/OXA-232 and blaNDM-5 were found in a high-risk clone, ST14 (n = 4). blaOXA-181/OXA-232 were in small, nonconjugative ColKP3 plasmids located on truncated Tn2013, whereas blaNDM-5 was in self-transmissible, conjugative IncFII plasmids, within truncated Tn125. Conjugal transfer of blaOXA-181/OXA-232 was observed in the presence of blaNDM-5. The study strains were diverse among themselves and showed various levels of relatedness with non-neonatal strains from different parts of the world and similarity with neonatal strains from Tanzania and Ghana when compared with a representative collection of carbapenemase-positive K. pneumoniae strains. We found that blaOXA-181/OXA-232-harboring isolates from a single neonatal unit had remarkably diverse genomes, ruling out clonal spread and emphasizing the extent of plasmid spreading across different STs. This study is probably the first to report the coexistence of blaOXA-181/232 and blaNDM-5 in neonatal isolates. IMPORTANCE Neonatal sepsis is a leading cause of neonatal mortality in low- and middle-income countries (LMICs). Treatment of sepsis in this vulnerable population is dependent on antimicrobials, and resistance to these life-saving antimicrobials is worrisome. Carbapenemases, enzymes produced by bacteria, can make these antimicrobials useless. Our study describes how OXA-48-like carbapenemases in neonatal septicemic Klebsiella pneumoniae shows remarkable diversity in the genomes of the strains and relatedness with strains from other parts of world and also to some neonatal outbreak strains. It is also the first to describe such resistance due to coproduction of dual carbapenemases, (OXA)-48 and New Delhi metallo-β-lactamase-5, in Klebsiella pneumoniae from neonatal settings. Carbapenemase genes situated on plasmids within high-risk international clones, as seen here, increase the ease and transfer of resistant genetic material. With the WHO treatment protocols not adequately poised to handle such infections, prompt attention to neonatal health care is required.

scholarly journals Colistin Resistance Among Multiple Sequence Types of Klebsiella pneumoniae Is Associated With Diverse Resistance Mechanisms: A Report From India

2021 ◽  
Vol 12 ◽  
Author(s):  
Mudsser Azam ◽  
Rajni Gaind ◽  
Gulshan Yadav ◽  
Amit Sharma ◽  
Kirti Upmanyu ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Klebsiella Pneumoniae ◽  
Transmembrane Protein ◽  
Bacterial Species ◽  
Regulatory System ◽  
Resistance Mechanisms ◽  
Clinical Samples ◽  
Colistin Resistance ◽  
Multiple Sequence ◽  
Sequence Types

Background: The resistance to colistin and carbapenems in Klebsiella pneumoniae infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance.Methods: Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system (phoPQ and pmrAB), regulatory transmembrane protein-coding mgrB, and mobilized colistin resistance genes (mcr-1-8). Gene expression of pmrC and pmrK was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools.Results: Of 335 Klebsiella spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). K. pneumoniae isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in phoP (T151A), phoQ (del87–90, del263–264, L30Q, and A351D), pmrA (G53S), pmrB (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and mgrB (C28G) genes. The mgrB gene in three strains was disrupted by insertion sequences encoding IS1-like and IS5/IS1182 family-like transposase genes. All 11 isolates showed an elevation in the transcription level of pmrC gene. Mobilized colistin-resistance (mcr) genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes blaNDM-1-like, blaOXA-48-like, and blaCTX-M-like were detected in eight, five, and nine isolates, respectively.Conclusion: All the studied colistin- and carbapenem-resistant K. pneumoniae isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species.

scholarly journals Diversity of International High-Risk Clones of Acinetobacter baumannii Revealed in a Russian Multidisciplinary Medical Center during 2017–2019

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1009
Author(s):  
Andrey Shelenkov ◽  
Lyudmila Petrova ◽  
Mikhail Zamyatin ◽  
Yulia Mikhaylova ◽  
Vasiliy Akimkin
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Acinetobacter Baumannii ◽  
Medical Center ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Epidemiological Surveillance ◽  
Genomic Epidemiology ◽  
Sequencing Technologies ◽  
The World

Acinetobacter baumannii is a dangerous bacterial pathogen possessing the ability to persist on various surfaces, especially in clinical settings, and to rapidly acquire the resistance to a broad spectrum of antibiotics. Thus, the epidemiological surveillance of A. baumannii within a particular hospital, region, and across the world is an important healthcare task that currently usually includes performing whole-genome sequencing (WGS) of representative isolates. During the past years, the dissemination of A. baumannii across the world was mainly driven by the strains belonging to two major groups called the global clones or international clones (ICs) of high risk (IC1 and IC2). However, currently nine ICs are already considered. Although some clones were previously thought to spread in particular regions of the world, in recent years this is usually not the case. In this study, we determined five ICs, as well as three isolates not belonging to the major ICs, in one multidisciplinary medical center within the period 2017–2019. We performed WGS using both short- and long-read sequencing technologies of nine representative clinical A. baumannii isolates, which allowed us to determine the antibiotic resistance and virulence genomic determinants, reveal the CRISPR/Cas systems, and obtain the plasmid structures. The phenotypic and genotypic antibiotic resistance profiles are compared, and the possible ways of isolate and resistance spreading are discussed. We believe that the data obtained will provide a better understanding of the spreading and resistance acquisition of the ICs of A. baumannii and further stress the necessity for continuous genomic epidemiology surveillance of this problem-causing bacterial species.

scholarly journals Hybrid Resistance and Virulence Plasmids in “High-Risk” Clones of Klebsiella pneumoniae, Including Those Carrying blaNDM-5

2019 ◽  
Vol 7 (9) ◽  
pp. 326 ◽  
Author(s):  
Jane Turton ◽  
Frances Davies ◽  
Jack Turton ◽  
Claire Perry ◽  
Zoë Payne ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Virulence Plasmid ◽  
Virulence Plasmids ◽  
Long Read ◽  
Multiple Resistance Genes ◽  
Sequence Types

Virulence plasmids are associated with hypervirulent types of Klebsiella pneumoniae, which generally do not carry antibiotic resistance genes. In contrast, nosocomial isolates are often associated with resistance, but rarely with virulence plasmids. Here, we describe virulence plasmids in nosocomial isolates of “high-risk” clones of sequence types (STs) 15, 48, 101, 147 and 383 carrying carbapenemase genes. The whole genome sequences were determined by long-read nanopore sequencing. The 12 isolates all contained hybrid plasmids containing both resistance and virulence genes. All carried rmpA/rmpA2 and the aerobactin cluster, with the virulence plasmids of two of three representatives of ST383 carrying blaNDM-5 and seventeen other resistance genes. Representatives of ST48 and ST15 had virulence plasmid-associated genes distributed between two plasmids, both containing antibiotic resistance genes. Representatives of ST101 were remarkable in all sharing virulence plasmids in which iucC and terAWXYZ were missing and iucB and iucD truncated. The combination of resistance and virulence in plasmids of high-risk clones is extremely worrying. Virulence plasmids were often notably consistent within a lineage, even in the absence of epidemiological links, suggesting they are not moving between types. However, there was a common segment containing multiple resistance genes in virulence plasmids of representatives of both STs 48 and 383.

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