scholarly journals Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae

2012 ◽  
Vol 4 (1) ◽  
pp. 33 ◽  
Author(s):  
Tarek A. Ahmad ◽  
Medhat Haroun ◽  
Ahmed A. Hussein ◽  
El Sayed H. El Ashry ◽  
Laila H. El-Sayed
Keyword(s):  
Klebsiella Pneumoniae ◽  
Respiratory Diseases ◽  
Capsular Polysaccharide ◽  
Outer Membrane Proteins ◽  
Immunological Methods ◽  
Easy Method ◽  
O Antigen ◽  
Bacterial Endotoxins ◽  
Tract Infections ◽  
Limited Spectrum

<em>Klebsiella pneumoniae</em> is a major cause of nosocomial pneumonia, septicemia and urinary tract infections, especially in newborns, blood cancer patients, and other immunocompromised candidates. The control of <em>K. pneumoniae</em> is a complicated issue due to its tight pathogenesis. Immuno-prophylactic preparations, especially those directed toward the <em>bacterium</em> O-antigen, showed to be the most successful way to prevent the infection incidence. However, all previously proposed preparations were either of limited spectrum or non-maternal, and hence not targeting the main <em>Klebsiella</em> patients. Moreover, all preparations were directed only to prevent the respiratory diseases due to that pathogen. This article addresses the development of a method originally used to purify the non-capsular bacterial- endotoxins, as a new and easy method for vaccine production against <em>K. pneumoniae</em>. The application of this method was preceded by a biotechnological control of capsular polysaccharide production in <em>K. pneumoniae</em>. The new produced natural conjugate between the bacterial O-antigen and its outer membrane proteins was evaluated by physicochemical and immunological methods to investigate its purity, integrity, safety and immunogenicity. It showed to be pure, stable, safe for use, and able to elicit a protective immunoglobulin titer against different <em>Klebsiella</em> infections. This immune-response proved to be transferable to the offspring of the vaccinated experimental rabbits via placenta.

scholarly journals Surface Antigen Exposure by Bismuth Dimercaprol Suppression of Klebsiella pneumoniae Capsular Polysaccharide

1999 ◽  
Vol 67 (2) ◽  
pp. 664-669 ◽  
Author(s):  
Philip Domenico ◽  
J. M. Tomas ◽  
S. Merino ◽  
X. Rubires ◽  
Burke A. Cunha
Keyword(s):  
Membrane Proteins ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Capsular Polysaccharide ◽  
Outer Membrane Proteins ◽  
Defined Medium ◽  
Phagocytic Index ◽  
Dependent Manner ◽  
O Antigen ◽  
Bacterial Capsule

ABSTRACT The bacterial capsule is an important virulence determinant in animal and plant disease. Bacterial capsule and slime can be inhibited by bismuth compounds, especially when complexed with lipophilic thiol chelators. Bismuth dimercaprol (BisBAL) at 1 ppm of Bi3+repressed Klebsiella pneumoniae capsule expression in defined medium by nearly 90%, which exposed subsurface structures. The phagocytic index for BisBAL-treated bacteria increased from <10 to 360 bacteria per 100 neutrophils in the presence of complement and anticapsular or anti-O antigen antiserum. BisBAL treatment also enhanced the reactivity of monoclonal antibodies (MAbs) specific for the O1-antigen lipopolysaccharide (LPS) or the LPS core in a dose-dependent manner as indicated by the results of enzyme-linked immunosorbent assays. When anti-O1 MAb was used, the reactivity increased significantly for fully encapsulated O1:K1 or O1:K2 cells but not for O1:K− cells. Deposition of C3b also increased significantly for BisBAL-treated O1:K1 or O1:K2 cells but not for O1:K− cells. Survival of a serum-sensitive strain was <0.1% when nonimmune human serum absorbed with O1:K1 cells was used and 107% when BisBAL-treated cells were used for absorption. Outer membrane proteins were also more accessible on the surface of K. pneumoniae after BisBAL treatment. Thus, at subinhibitory levels, BisBAL inhibited capsule expression, which promoted phagocytosis, enhanced the reactivity of specific antibodies for LPS O antigen, LPS core epitopes, or outer-membrane proteins, and enhanced complement interaction with encapsulated K. pneumoniae. By unmasking bacterial surface structures and enhancing the immune system reactivity to bacteria, bismuth thiols may prove useful as adjuncts for vaccination.

scholarly journals A Gene, uge, Is Essential for Klebsiella pneumoniae Virulence

2004 ◽  
Vol 72 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Miguel Regué ◽  
Beatriz Hita ◽  
Nuria Piqué ◽  
Luis Izquierdo ◽  
Susana Merino ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Animal Models ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Outer Core ◽  
Single Mutation ◽  
Wild Type ◽  
Core Oligosaccharide ◽  
O Antigen ◽  
Tract Infections

ABSTRACT Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the surface. A single mutation in a gene that codes for a UDP galacturonate 4-epimerase (uge) renders a strain with the O−:K− phenotype (lack of capsule and LPS without O antigen molecules and outer core oligosaccharide). The uge gene was present in all the K. pneumoniae strains tested. The K. pneumoniae uge mutants were unable to produce experimental urinary tract infections in rats and were completely avirulent in two different animal models (septicemia and pneumonia). Reintroduction of the single uge wild-type gene in the corresponding mutants completely restored the wild-type phenotype (presence of capsule and smooth LPS) independently of the O or K serotype of the wild type. Furthermore, complemented uge mutants recovered the ability to produce experimental urinary tract infections in rats and virulence in the septicemia and pneumonia animal models.

scholarly journals The KbvR Regulator Contributes to Capsule Production, Outer Membrane Protein Biosynthesis, Antiphagocytosis, and Virulence in Klebsiella pneumoniae

2021 ◽  
Vol 89 (5) ◽  
Author(s):  
Li Xu ◽  
Meng Wang ◽  
Jie Yuan ◽  
Hui Wang ◽  
Moran Li ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane ◽  
Capsular Polysaccharide ◽  
Protein Biosynthesis ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Innate Immune ◽  
Content Type

ABSTRACT Klebsiella pneumoniae is an opportunistic pathogen that mostly affects patients with weakened immune systems, but a few serotypes (especially K1 and K2) are highly invasive and result in systemic infection in healthy persons. The ability to evade and survive the components of the innate immune system is critical in infection. To investigate the role and mechanism of transcription regulator KP1_RS12260 (KbvR) in virulence and defense against the innate immune response, kbvR deletion mutant and complement strains were constructed. The in vivo animal infection assay and in vitro antiphagocytosis assay demonstrate K. pneumoniae KbvR is an important regulator that contributes to virulence and the defense against phagocytosis of macrophages. The transcriptome analysis and phenotype experiments demonstrated that deletion of kbvR decreased production of capsular polysaccharide (CPS) and biosynthesis of partly outer membrane proteins (OMPs). The findings suggest that KbvR is a global regulator that confers pathoadaptive phenotypes, which provide several implications for improving our understanding of the pathogenesis of K. pneumoniae.

scholarly journals Whole Genome Sequencing of Pediatric Klebsiella pneumoniae Strains Reveals Important Insights Into Their Virulence-Associated Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Mauricio Flores-Valdez ◽  
Miguel A. Ares ◽  
Roberto Rosales-Reyes ◽  
Javier Torres ◽  
Jorge A. Girón ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Outer Membrane Proteins ◽  
Multi Drug Resistance ◽  
Phylogenomic Analysis ◽  
Whole Genome ◽  
Clustering Methods ◽  
Genes Encoding ◽  
Tract Infections

Klebsiella pneumoniae is recognized as a common cause of nosocomial infections and outbreaks causing pneumonia, septicemia, and urinary tract infections. This opportunistic bacterium shows an increasing acquisition of antibiotic-resistance genes, which complicates treatment of infections. Hence, fast reliable strain typing methods are paramount for the study of this opportunistic pathogen’s multi-drug resistance genetic profiles. In this study, thirty-eight strains of K. pneumoniae isolated from the blood of pediatric patients were characterized by whole-genome sequencing and genomic clustering methods. Genes encoding β-lactamase were found in all the bacterial isolates, among which the blaSHV variant was the most prevalent (53%). Moreover, genes encoding virulence factors such as fimbriae, capsule, outer membrane proteins, T4SS and siderophores were investigated. Additionally, a multi-locus sequence typing (MLST) analysis revealed 24 distinct sequence types identified within the isolates, among which the most frequently represented were ST76 (16%) and ST70 (11%). Based on LPS structure, serotypes O1 and O3 were the most prevalent, accounting for approximately 63% of all infections. The virulence capsular types K10, K136, and K2 were present in 16, 13, and 8% of the isolates, respectively. Phylogenomic analysis based on virtual genome fingerprints correlated with the MLST data. The phylogenomic reconstruction also denoted association between strains with a higher abundance of virulence genes and virulent serotypes compared to strains that do not possess these traits. This study highlights the value of whole-genomic sequencing in the surveillance of virulence attributes among clinical K. pneumoniae strains.

The influence of lipopolysaccharide on the transformation efficiency of Klebsiella pneumoniae

1989 ◽  
Vol 35 (7) ◽  
pp. 735-737 ◽  
Author(s):  
Silvia Camprubí ◽  
Miquel Regué ◽  
Juán Tomás
Keyword(s):  
Klebsiella Pneumoniae ◽  
Significant Influence ◽  
Capsular Polysaccharide ◽  
Transformation Efficiency ◽  
Transformation Procedure ◽  
O Antigen

The presence of O antigen of the lipopolysaccharide on Klebsiella pneumoniae is responsible for the low transformation frequencies observed. No significant influence of capsular polysaccharide could be observed. This phenomenon was independent of the transformation procedure and plasmid size.Key words: lipopolysaccharide, capsular polysaccharide, transformation, Klebsiella pneumoniae.

scholarly journals The Impact of Insertion Sequences on O-Serotype Phenotype and Its O-Locus-Based Prediction in Klebsiella pneumoniae O2 and O1

2020 ◽  
Vol 21 (18) ◽  
pp. 6572
Author(s):  
Daria Artyszuk ◽  
Radosław Izdebski ◽  
Anna Maciejewska ◽  
Marta Kaszowska ◽  
Aleksandra Herud ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Capsular Polysaccharide ◽  
Passive Immunization ◽  
In Silico Analysis ◽  
Clinical Isolates ◽  
Insertion Sequences ◽  
O Antigen ◽  
O Antigens ◽  
The Impact ◽  
K Antigen

Klebsiella pneumoniae is a nosocomial pathogen, pointed out by the World Helth Organisation (WHO) as “critical” regarding the highly limited options of treatment. Lipopolysaccharide (LPS, O-antigen) and capsular polysaccharide (K-antigen) are its virulence factors and surface antigens, determining O- and K-serotypes and encoded by O- or K-loci. They are promising targets for antibody-based therapies (vaccines and passive immunization) as an alternative to antibiotics. To make such immunotherapy effective, knowledge about O/K-antigen structures, drift, and distribution among clinical isolates is needed. At present, the structural analysis of O-antigens is efficiently supported by bioinformatics. O- and K-loci-based genotyping by polymerase chain reaction (PCR) or whole genome sequencing WGS has been proposed as a diagnostic tool, including the Kaptive tool available in the public domain. We analyzed discrepancies for O2 serotyping between Kaptive-based predictions (O2 variant 2 serotype) and the actual phenotype (O2 variant 1) for two K. pneumoniae clinical isolates. Identified length discrepancies from the reference O-locus resulted from insertion sequences (ISs) within rfb regions of the O-loci. In silico analysis of 8130 O1 and O2 genomes available in public databases indicated a broader distribution of ISs in rfbs that may influence the actual O-antigen structure. Our results show that current high-throughput genotyping algorithms need to be further refined to consider the effects of ISs on the LPS O-serotype.

Indirect Determination of Amikacin by Gold Nanoparticles as Redox Probe

2020 ◽  
Vol 17 ◽  
Author(s):  
Mansureh Alizadeh ◽  
Mandana Amiri ◽  
Abolfazl Bezaatpour
Keyword(s):  
Gold Nanoparticles ◽  
Bacterial Infections ◽  
Limit Of Detection ◽  
Pharmaceutical Preparation ◽  
Cathodic Peak ◽  
Easy Method ◽  
Peak Current ◽  
Indirect Determination ◽  
Tract Infections

: Amikacin is an aminoglycoside antibiotic used for many gram-negative bacterial infections like infections in the urinary tract, infections in brain, lungs and abdomen. Electrochemical determination of amikacin is a challenge in electroanalysis because it shows no voltammetric peak at the surface of bare electrodes. In this approach, a very simple and easy method for indirect voltammetric determination of amikacin presented in real samples. Gold nanoparticles were electrodeposited at the surface of glassy carbon electrode in constant potential. The effect of several parameters such as time and potential of deposition, pH and scan rates on signal were studied. The cathodic peak current of Au3+ decreased with increasing amikacin concentration. Quantitative analysis of amikacin was performed using differential pulse voltammetry by following cathodic peak current of gold ions. Two dynamic linear ranges of 1.0 × 10−8–1.0 × 10-7 M and 5.0 × 10−7–1.0 × 10-3 M were obtained and limit of detection was estimated 3.0× 10−9 M. The method was successfully determined amikacin in pharmaceutical preparation and human serum. The effect of several interference in determination of amikacin was also studied.

scholarly journals Molecular Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Urine at a Teaching Hospital in Taiwan

2021 ◽  
Vol 9 (2) ◽  
pp. 271
Author(s):  
Yuarn-Jang Lee ◽  
Chih-Hung Huang ◽  
Noor Andryan Ilsan ◽  
I-Hui Lee ◽  
Tzu-Wen Huang
Keyword(s):  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Pcr Analysis ◽  
Carbapenem Resistant ◽  
High Prevalence ◽  
Antimicrobial Susceptibility Tests ◽  
Susceptibility Tests ◽  
Tract Infections

Urinary tract infections (UTIs) are common in clinics and hospitals and are associated with a high economic burden. Enterobacterium Klebsiella pneumoniae is a prevalent agent causing UTIs. A high prevalence of carbapenem-resistant K. pneumoniae (CRKP) has emerged recently and is continuing to increase. Seventeen urinary CRKP isolates collected at a teaching hospital in Taiwan from December 2016 to September 2017 were analyzed to elucidate their drug resistance mechanisms. Two-thirds of the isolates were obtained from outpatients. Antimicrobial susceptibility tests demonstrated multidrug resistance in all the isolates. Multilocus sequence typing analysis showed high diversity among the isolates. PCR analysis demonstrated the presence of carbapenemases in three isolates. All isolates carried at least one other extended-spectrum β-lactamase, including TEM, DHA, and CTX-M. Fifteen isolates contained mutations in one of the outer membrane porins that were assessed. The expression levels of the acrB and/or oqxB efflux pump genes, as determined by qRT-PCR, were upregulated in 11 isolates. Six isolates might have utilized other efflux pumps or antimicrobial resistance mechanisms. These analyses demonstrated a highly diverse population and the presence of complex resistance mechanisms in urinary isolates of K. pneumoniae.

scholarly journals 1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen
Keyword(s):  
United States ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Antibiotic Use ◽  
The United States ◽  
Drug Resistant ◽  
E Coli ◽  
Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

Sign in / Sign up

Export Citation Format

Share Document