The contribution of capsule polysaccharide genes to virulence of <i>Klebsiella pneumoniae</i>

Ko, Kwan Soo

doi:10.1080/21505594.2016.1240862

Cited by 38 publications

(41 citation statements)

References 16 publications

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“…In the K. pneumoniae genome, the cps locus, encoding the capsular polysaccharide outer layer, is a recognized recombination hotspot, responsible for the diversification of clonal lineages, particularly within the CG258 group (6-8), and over 100 capsular types have been identified in this species (42,46). The capsule is a complex structure of repeating sugar subunits that protects the cell from external threats (including phage attack) and enhances K. pneumoniae virulence, being implicated in resistance to host defence mechanisms, immune evasion, adherence, and biofilm formation (47). K. pneumoniae types produce capsule in varying degrees and hypermucoviscosity (excessive capsule production) has been linked to increased virulence (47).…”

Section: Discussionmentioning

confidence: 99%

“…The capsule is a complex structure of repeating sugar subunits that protects the cell from external threats (including phage attack) and enhances K. pneumoniae virulence, being implicated in resistance to host defence mechanisms, immune evasion, adherence, and biofilm formation (47). K. pneumoniae types produce capsule in varying degrees and hypermucoviscosity (excessive capsule production) has been linked to increased virulence (47). In our study, we identified three novel capsular variants in ST258 clade 1 due to ISKpn 26 insertion in the cps locus, and responsible for the intra-clade variation in our population which correlated remarkably well with reduced host range for many of the clade 1 infecting phages.…”

Section: Discussionmentioning

confidence: 99%

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K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Venturini

Zakour

Bowring

et al. 2019

Preprint

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24Multidrug resistant carbapenemase-producing Klebsiella pneumoniae capable of causing 25 severe disease in humans is classified as an urgent threat by health agencies worldwide. 26 Bacteriophages are being actively explored as potential therapeutics against these multidrug 27 resistant pathogens. We are currently developing bacteriophage therapy against carbepenem-28 resistant K. pneumoniae belonging to the genetically diverse, globally disseminated clonal 29 group CG258. In an effort to define a robust experimental approach for effective selection of 30 lytic viruses for therapy, we have fully characterized the bacterial genomes of 18 target 31 strains, tested them against novel lytic bacteriophages, and generated phage-susceptibility 32 profiles. The genomes of K. pneumoniae isolates carrying blaNDM and blaKPC were sequenced 33 and isolates belonging to CG258 were selected for susceptibility testing using a panel of lytic 34 bacteriophages (n=65). The local K. pneumoniae CG258 population was dominated by 35 isolates belonging to sequence type ST258 clade 1 (86%). The primary differences between 36 ST258 genomes were variations in the capsular locus (cps) and in prophage content. We 37 showed that CG258-specific lytic phages primarily target the capsule, and that successful 38 infection is blocked in many, post-adsorption, by immunity conferred by existing prophages. 39Five bacteriophages specifically active against K. pneumoniae ST258 clade 1 (n=5) 40 belonging to the Caudovirales order were selected for further characterization. Our findings 41 show that effective control of K. pneumoniae CG258 with phage will require mixes of 42 diverse lytic viruses targeting all relevant cps variants and allowing for variable prophage 43 content. These insights will facilitate identification and selection of therapeutic phage 44 candidates against this serious pathogen. 45 46 47 48 Importance 49Bacteriophages are natural agents that exclusively and selectively kill bacteria and have the 50 potential to be useful in the treatment of multidrug resistant infections. K. pneumoniae 51 CG258 is a main agent of life-threatening sepsis that is often resistant to last-line antibiotics. 52Our work highlights some key requirements for developing bacteriophage preparations 53 targeting this pathogen. By defining the genomic profile of our clinical K. pneumoniae 54 CG258 population and matching it with bacteriophage susceptibility patterns, we found that 55 bacteriophage ability to lyse each strain correlates well with K. pneumoniae CG258 structural 56 subtypes (capsule variants). This indicates that preparation of bacteriophage therapeutics 57 targeting this pathogen should aim at including phages against each bacterial capsular 58 subtype. This necessitates a detailed understanding of the diversity of circulating isolates in 59 different geographical areas in order to make rational therapeutic choices. 60 61 62 Klebsiella pneumoniae is an important ubiquitous Gram-negative species capable of causing 63 disease in both humans an...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Venturini

Zakour

Bowring

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…It is found in the environment, as well as soil and surface water. K. pneumoniae colonizes human mucosal surfaces and spreads rapidly to other tissues leading to nosocomial infections in hospital settings, multidrug-resistance and high morbidity and mortality rates [53,61]. The Gram-negative bacteria P. mirabilis is a rod-shaped bacillus, which is facultatively anaerobic and has swarming motility [51,53].…”

Section: Agar Well and Disc Diffusion Assaysmentioning

confidence: 99%

“…Streptomycin inhibits the bacterial protein synthesis leading to the death of microbial cells. It is used as a broad-spectrum antibiotic against Gram-positive and Gram-negative bacteria [51,60,61]. The spore-forming bacteria B. subtilis was inhibited by streptomycin (ZOI = 22 mm), more effectively than by [Na(12-crown-4) 2 ]I 3 (10 mm).…”

Section: Antibiotic Screening Testsmentioning

confidence: 99%

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“Smart” Triiodide Compounds: Does Halogen Bonding Influence Antimicrobial Activities?

et al. 2019

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Antimicrobial agents containing symmetrical triiodides complexes with halogen bonding may release free iodine molecules in a controlled manner. This happens due to interactions with the plasma membrane of microorganisms which lead to changes in the structure of the triiodide anion. To verify this hypothesis, the triiodide complex [Na(12-crown-4)2]I3 was prepared by an optimized one-pot synthesis and tested against 18 clinical isolates, 10 reference strains of pathogens and five antibiotics. The antimicrobial activities of this symmetrical triiodide complex were determined by zone of inhibition plate studies through disc- and agar-well-diffusion methods. The triiodide complex proved to be a broad spectrum microbicidal agent. The biological activities were related to the calculated partition coefficient (octanol/water). The microstructural analysis of SEM and EDS undermined the purity of the triiodide complex. The anionic structure consists of isolated, symmetrical triiodide anions [I-I-I]- with halogen bonding. Computational methods were used to calculate the energy required to release iodine from [I-I-I]- and [I-I···I]-. The halogen bonding in the triiodide ion reduces the antibacterial activities in comparison to the inhibitory actions of pure iodine but increases the long term stability of [Na(12-crown-4)2]I3.

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Potential mechanism of gallic acid‐coated iron oxide nanoparticles against associated genes of Klebsiella pneumoniae capsule, antibacterial and antibiofilm

Khaleel,

Mutter,

Huang

2024

Microscopy Res & Technique

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Antibiotic resistance has increased in recent years, especially for pathogens like Klebsiella pneumoniae. Discovering and developing new drugs is challenging due to the high resistance of pathogens. Metal nanoparticles have been widely used in recent years to overcome and treat infections. Gallic acid‐coated iron oxide nanoparticles (IONPs‐GA) were synthesized in a simple and cost‐effective method. The morphology characteristics of synthesized IONPs‐GA were analyzed using Fourier transform infrared spectroscopy (FTIR), x‐ray diffraction analysis (XRD), and scanning electron microscope (SEM) analysis. IONPs were mostly spherical in shape with sizes ranging between 32 and 61 nm. All analyses used in this study confirmed the successful coating of gallic acid to iron oxide. Biological activities were studied phenotypically and on the molecular level, including antibacterial, antibiofilm, and mRNA levels of capsule‐associated genes. The results showed high antimicrobial activity of the synthesized nanoparticles against different G+ve and G−ve bacteria. The highest activity was recorded against Staphylococcus aureus (43 mm) and K. pneumoniae (22 mm). The MIC of IONPs against K. pneumoniae was 3.12 mg/mL and SEM analysis showed adhering the IONPs‐GA to the cell surface of K. pneumoniae resulted in disrupting the cell membrane. Different concentrations of sub‐MIC inhibited K. pneumoniae biofilm formation with the highest inhibition percentage at ½ × MIC (66.86%). Also, the synthesized IONPs‐GA differently affected the regulation and mRNA level of capsule‐associated genes in K. pneumoniae. The results indicated that IONPs‐GA could be useful in biological applications such as in drug delivery and treatment wide range of pathogens.Research Highlights Gallic acid was successfully coated into iron oxide nanoparticles synthesized in a simple way. IONPs‐GA was morphologically characterized using FTIR, XRD, and SEM. Evaluation the activity of IONPs‐GA as antibacterial, antibiofilm, and study the potential level of mRNA affected by IONPs‐GA

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The contribution of capsule polysaccharide genes to virulence of Klebsiella pneumoniae

Cited by 38 publications

References 16 publications

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

“Smart” Triiodide Compounds: Does Halogen Bonding Influence Antimicrobial Activities?

Potential mechanism of gallic acid‐coated iron oxide nanoparticles against associated genes of Klebsiella pneumoniae capsule, antibacterial and antibiofilm

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