Klebsiella pneumoniae capsule polysaccharide as a target for therapeutics and vaccines

Opoku‐Temeng, Clement; Kobayashi, Scott D.; DeLeo, Frank R.

doi:10.1016/j.csbj.2019.09.011

Cited by 79 publications

(56 citation statements)

References 86 publications

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“…Recently, many reports studying polysaccharides of natural origin have indicated that there are a variety of biological functions, such as anti-tumor, immune stimulation, antibacterial, anti-oxidant, with various polysaccharides (Song et al, 2008;Chen et al, 2010Chen et al, , 2019Opoku-Temeng et al, 2019;. The antitumor effect of these polysaccharides is mainly exerted by regulating the host's immune function.…”

Section: Discussionmentioning

confidence: 99%

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Chu

Miao

Huang

et al. 2020

Front. Bioeng. Biotechnol.

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Objective: This work is to study the effect of Rhizopus nigrum polysaccharide EPS1-1 on hepatocellular carcinoma (HCC) in vitro and in vivo. Methods: HepG2 and Huh-7 cells and nude mice models of liver cancers were used in this study. The cells and nude mice were treated with EPS1-1 at different concentrations. The CCK8 assays were used to measure the proliferation activities of cells, apoptosis was determined with flow cytometry, cell migration was measured by wound-healing assays, cell invasion was evaluated by Transwell assay, and the survival periods of different groups of tumor-bearing mice were compared. Real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins of the genes related to proliferation, apoptosis, migration, and invasion. Results: In vitro experiments revealed that when treated with EPS1-1, HepG2 and Huh-7 cell proliferation activities decreased, while there was an increase for the apoptosis rate, and the migration and invasion capabilities were significantly reduced. In vivo experiments showed that EPS1-1 could significantly reduce the tumor growth and lung metastasis of HCC, and prolong the survival periods of tumor-bearing nude mice. Furthermore, EPS1-1 has no apparent damage to the heart, liver, and kidney. Further studies showed that EPS1-1 could affect the expression of proliferation-related genes CCND1 and c-Myc, apoptosis-related genes BAX and Bcl-2, and migration and invasion related genes Vimentin and Slug, thereby affecting the biological process of HCC. Conclusion: EPS1-1 can inhibit the malignant process of HCC in vitro and in vivo, which indicates that EPS1-1 has the potential value of clinical application as chemotherapy or adjuvant in the treatment of liver cancer.

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Section: Discussionmentioning

confidence: 99%

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Chu

Miao

Huang

et al. 2020

Front. Bioeng. Biotechnol.

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“…The polysaccharide capsule of K. pneumoniae protects the pathogen from host cellmediated killing and the bactericidal effect of serum, thus contributing to K. pneumoniae pathogenicity (12). Studies examining the efficacy of antibodies (Abs) directed against CR-Kp CPS have demonstrated their potency in human cells and animal models (13)(14)(15)(16)(17), and CPS vaccines have the potential to prevent or moderate the severity of CR-Kp infection in monkeys and decrease the prevalence and emergence of resistant strains (14,(18)(19)(20). However, it is unknown if natural antibody responses to K. pneumoniae rely on anticapsular responses.…”

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confidence: 99%

Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

Banerjee

Motley

Diago-Navarro

et al. 2021

mSphere

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Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.

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“…The rise in carbapenem-resistant K. pneumoniae infections in hospitals and its associated morbidity and mortality 43 has led to increased interest in alternative control strategies such as vaccines, phage therapy and antibody therapy, key targets for which are the K and O surface antigens 44,45 . Kleborate confidently identified K and O biosynthesis loci in 98.3% and 99.1% of EuSCAPE genomes, respectively, including 87 distinct K loci and 11 distinct O loci ( Figures S2 and S3 ).…”

Section: Resultsmentioning

confidence: 99%

Genomic surveillance framework and global population structure forKlebsiella pneumoniae

Mmc

et al. 2020

Preprint

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K. pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes.

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Klebsiella pneumoniae capsule polysaccharide as a target for therapeutics and vaccines

Abstract: Graphical abstract

Cited by 79 publications

References 86 publications

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

Genomic surveillance framework and global population structure forKlebsiella pneumoniae

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