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.

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 New Bacteriophages against Emerging Lineages ST23 and ST258 of Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 411 ◽  
Author(s):  
Damien Thiry ◽  
Virginie Passet ◽  
Katarzyna Danis-Wlodarczyk ◽  
Cédric Lood ◽  
Jeroen Wagemans ◽  
...  
Keyword(s):  
Public Health ◽  
Mortality Rate ◽  
Klebsiella Pneumoniae ◽  
Phage Therapy ◽  
Galleria Mellonella ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Multiplicity Of Infection ◽  
Public Health Importance ◽  
Efficacy Assessment

Klebsiella pneumoniae is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and assess their potential to control infections by the ST23 and ST258 K. pneumoniae sublineages using a Galleria mellonella larvae model. Three selected bacteriophages, targeting lineages ST258 (bacteriophages vB_KpnP_KL106-ULIP47 and vB_KpnP_KL106-ULIP54) and ST23 (bacteriophage vB_KpnP_K1-ULIP33), display specificity for capsular types KL106 and K1, respectively. These podoviruses belong to the Autographivirinae subfamily and their genomes are devoid of lysogeny or toxin-associated genes. In a G. mellonella larvae model, a mortality rate of 70% was observed upon infection by K. pneumoniae ST258 and ST23. This number was reduced to 20% upon treatment with bacteriophages at a multiplicity of infection of 10. This work increases the number of characterized bacteriophages infecting K. pneumoniae and provides information regarding genome sequence and efficacy during preclinical phage therapy against two prominent sublineages of this bacterial species.

scholarly journals Identification and elimination of genomic regions irrelevant for magnetosome biosynthesis by large-scale deletion in Magnetospirillum gryphiswaldense

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Theresa Zwiener ◽  
Frank Mickoleit ◽  
Marina Dziuba ◽  
Christian Rückert ◽  
Tobias Busche ◽  
...  
Keyword(s):  
Genome Editing ◽  
Large Scale ◽  
Gene Clusters ◽  
Genomic Region ◽  
Gene Content ◽  
Neighboring Gene ◽  
Magnetospirillum Gryphiswaldense ◽  
Replacement Method ◽  
Full Complement ◽  
Genomic Regions

Abstract Background Magnetosome formation in the alphaproteobacterium Magnetospirillum gryphiswaldense is controlled by more than 30 known mam and mms genes clustered within a large genomic region, the ‘magnetosome island’ (MAI), which also harbors numerous mobile genetic elements, repeats, and genetic junk. Because of the inherent genetic instability of the MAI caused by neighboring gene content, the elimination of these regions and their substitution by a compact, minimal magnetosome expression cassette would be important for future analysis and engineering. In addition, the role of the MAI boundaries and adjacent regions are still unclear, and recent studies indicated that further auxiliary determinants for magnetosome biosynthesis are encoded outside the MAI. However, techniques for large-scale genome editing of magnetic bacteria are still limited, and the full complement of genes controlling magnetosome formation has remained uncertain. Results Here we demonstrate that an allelic replacement method based on homologous recombination can be applied for large-scale genome editing in M. gryphiswaldense. By analysis of 24 deletion mutants covering about 167 kb of non-redundant genome content, we identified genes and regions inside and outside the MAI irrelevant for magnetosome biosynthesis. A contiguous stretch of ~ 100 kb, including the scattered mam and mms6 operons, could be functionally substituted by a compact and contiguous ~ 38 kb cassette comprising all essential biosynthetic gene clusters, but devoid of interspersing irrelevant or problematic gene content. Conclusions Our results further delineate the genetic complement for magnetosome biosynthesis and will be useful for future large-scale genome editing and genetic engineering of magnetosome biosynthesis.

scholarly journals Development of an Immunochromatographic Strip Using Conjugated Gold Nanoparticles for the Rapid Detection of Klebsiella pneumoniae Causing Neonatal Sepsis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1141
Author(s):  
Noha M. Elhosseiny ◽  
Tamer M. Samir ◽  
Aliaa A. Ali ◽  
Amani A. El-Kholy ◽  
Ahmed S. Attia
Keyword(s):  
Gold Nanoparticles ◽  
Klebsiella Pneumoniae ◽  
Causative Agent ◽  
Neonatal Sepsis ◽  
Bacterial Species ◽  
Resistant Bacteria ◽  
Immunochromatographic Strip ◽  
Amino Acid Peptide ◽  
Negative Results ◽  
Drug Resistant Bacteria

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and the spread of multi-drug-resistant bacteria. In this work, we deployed bioinformatics and proteomics analyses to determine a promising target that could be used for the identification of a major neonatal sepsis causative agent, Klebsiella pneumoniae. A 19 amino acid peptide from a hypothetical outer membrane was found to be very specific to the species, well conserved among its strains, surface exposed, and expressed in conditions simulating infection. Antibodies against the selected peptide were conjugated to gold nanoparticles and incorporated into an immunochromatographic strip. The developed strip was able to detect as low as 105 CFU/mL of K. pneumoniae. Regarding specificity, it showed negative results with both Escherichia coli and Enterobacter cloacae. More importantly, in a pilot study using neonatal sepsis cases blood specimens, the developed strip selectively gave positive results within 20 min with those infected with K. pneumoniae without prior sample processing. However, it gave negative results in cases infected with other bacterial species.

scholarly journals Phage Resistance Is Associated with Decreased Virulence in KPC-Producing Klebsiella pneumoniae of the Clonal Group 258 Clade II Lineage

2021 ◽  
Vol 9 (4) ◽  
pp. 762
Author(s):  
Lucia Henrici De Angelis ◽  
Noemi Poerio ◽  
Vincenzo Di Pilato ◽  
Federica De Santis ◽  
Alberto Antonelli ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Parental Strain ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Galleria Mellonella ◽  
Bacterial Pathogen ◽  
Phage Resistance ◽  
Infection Model ◽  
Lytic Phage ◽  
Susceptible Host

Phage therapy is now reconsidered with interest in the treatment of bacterial infections. A major piece of information for this application is the definition of the molecular targets exploited by phages to infect bacteria. Here, the genetic basis of resistance to the lytic phage φBO1E by its susceptible host Klebsiella pneumoniae KKBO-1 has been investigated. KKBO-1 phage-resistant mutants were obtained by infection at high multiplicity. One mutant, designated BO-FR-1, was selected for subsequent experiments, including virulence assessment in a Galleria mellonella infection model and characterization by whole-genome sequencing. Infection with BO-FR-1 was associated with a significantly lower mortality when compared to that of the parental strain. The BO-FR-1 genome differed from KKBO-1 by a single nonsense mutation into the wbaP gene, which encodes a glycosyltransferase involved in the first step of the biosynthesis of the capsular polysaccharide (CPS). Phage susceptibility was restored when BO-FR-1 was complemented with the constitutive wbaP gene. Our results demonstrated that φBO1E infects KKBO-1 targeting the bacterial CPS. Interestingly, BO-FR-1 was less virulent than the parental strain, suggesting that in the context of the interplay among phage, bacterial pathogen and host, the emergence of phage resistance may be beneficial for the host.

scholarly journals 3D reconstruction of genomic regions from sparse interaction data

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Julen Mendieta-Esteban ◽  
Marco Di Stefano ◽  
David Castillo ◽  
Irene Farabella ◽  
Marc A Marti-Renom
Keyword(s):  
3D Models ◽  
Genomic Region ◽  
Gene Promoters ◽  
Chromosome Conformation ◽  
The Matrix ◽  
Chromatin Structural ◽  
A Cell ◽  
Similar Accuracy ◽  
Genomic Regions ◽  
Interaction Matrices

Abstract Chromosome conformation capture (3C) technologies measure the interaction frequency between pairs of chromatin regions within the nucleus in a cell or a population of cells. Some of these 3C technologies retrieve interactions involving non-contiguous sets of loci, resulting in sparse interaction matrices. One of such 3C technologies is Promoter Capture Hi-C (pcHi-C) that is tailored to probe only interactions involving gene promoters. As such, pcHi-C provides sparse interaction matrices that are suitable to characterize short- and long-range enhancer–promoter interactions. Here, we introduce a new method to reconstruct the chromatin structural (3D) organization from sparse 3C-based datasets such as pcHi-C. Our method allows for data normalization, detection of significant interactions and reconstruction of the full 3D organization of the genomic region despite of the data sparseness. Specifically, it builds, with as low as the 2–3% of the data from the matrix, reliable 3D models of similar accuracy of those based on dense interaction matrices. Furthermore, the method is sensitive enough to detect cell-type-specific 3D organizational features such as the formation of different networks of active gene communities.

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 Moraxella catarrhalis: from Emerging to Established Pathogen

2002 ◽  
Vol 15 (1) ◽  
pp. 125-144 ◽  
Author(s):  
Cees M. Verduin ◽  
Cees Hol ◽  
André Fleer ◽  
Hans van Dijk ◽  
Alex van Belkum
Keyword(s):  
Moraxella Catarrhalis ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Diagnostic Techniques ◽  
Human Infection ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Pathogenic Potential ◽  
The Past

SUMMARY Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of Β-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

scholarly journals Relationship between Yield Components and Partial Resistance to Lecanicillium fungicola in the Button Mushroom, Agaricus bisporus, Assessed by Quantitative Trait Locus Mapping

2012 ◽  
Vol 78 (7) ◽  
pp. 2435-2442 ◽  
Author(s):  
Marie Foulongne-Oriol ◽  
Anne Rodier ◽  
Jean-Michel Savoie
Keyword(s):  
Quantitative Trait ◽  
Wild Strain ◽  
Genomic Region ◽  
Yield Component ◽  
Phenotypic Variance ◽  
Button Mushroom ◽  
Content Type ◽  
Dry Bubble ◽  
Trait Locus ◽  
Genomic Regions

ABSTRACTDry bubble, caused byLecanicillium fungicola, is one of the most detrimental diseases affecting button mushroom cultivation. In a previous study, we demonstrated that breeding for resistance to this pathogen is quite challenging due to its quantitative inheritance. A second-generation hybrid progeny derived from an intervarietal cross between a wild strain and a commercial cultivar was characterized forL. fungicolaresistance under artificial inoculation in three independent experiments. Analysis of quantitative trait loci (QTL) was used to determine the locations, numbers, and effects of genomic regions associated with dry-bubble resistance. Four traits related to resistance were analyzed. Two to four QTL were detected per trait, depending on the experiment. Two genomic regions, on linkage group X (LGX) and LGVIII, were consistently detected in the three experiments. The genomic region on LGX was detected for three of the four variables studied. The total phenotypic variance accounted for by all QTL ranged from 19.3% to 42.1% over all traits in all experiments. For most of the QTL, the favorable allele for resistance came from the wild parent, but for some QTL, the allele that contributed to a higher level of resistance was carried by the cultivar. Comparative mapping with QTL for yield-related traits revealed five colocations between resistance and yield component loci, suggesting that the resistance results from both genetic factors and fitness expression. The consequences for mushroom breeding programs are discussed.

scholarly journals Antioxidative and antimicrobial potentials of Parmelia saxatilis and Pseudoevernia furfuracea

2016 ◽  
pp. 9-18
Author(s):  
Jasmina Cilerdzic ◽  
Mirjana Stajic ◽  
Jelena Vukojevic
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Side Effects ◽  
Klebsiella Pneumoniae ◽  
Bacterial Species ◽  
Phenol Content ◽  
Negative Side Effects ◽  
Highly Correlated ◽  
Ethanol Extracts

Even though numerous lichen species possess significant medical potentials they are still unexplored, and particularly species and strains originating from Serbia. Therefore, the aim of this study was to evaluate the antioxidative and antimicrobial potential of ethanol extracts of Parmelia saxatilis and Pseudoevernia furfuracea collected in Serbia. The tested extracts were good scavengers of DPPH radicals, with capacities ranging from 14.76% to 79.76% in P. saxatilis and from 21.39% to 90.04% in P. furfuracea. In P. saxatilis level of DPPH? neutralisation was highly correlated with phenol content (r2 = 0.9981) and in P. furfuracea with amount of total flavonoides (r2 = 0.9641). The extract of P. furfuracea inhibited the growth of all tested microorganisms with exception of Aspergillus flavus, while P. saxatilis extract affected only growth of bacterial species. Among tested microorganisms, Staphylococcus aureus and Klebsiella pneumoniae were the most sensitive, while Enterococcus faecalis, Pseudomonas aeruginosa as well as micromycetes were the least sensitive to tested extracts. Because of these potentials and the fact that their long term usage does not have any negative side effects on organism and development of microbial resistance, the extracts could be included in conventional therapy.

Sign in / Sign up

Export Citation Format

Share Document