Immunogenic characteristics of the outer membrane phosphoporin as a vaccine candidate against Klebsiella pneumoniae

Hu, Gaowei; Chen, Xue; Chu, Wenhui; Ma, Zhe; Miao, Yingjie; Luo, Xi; Fu, Yongqian

doi:10.1186/s13567-022-01023-2

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…Mice immunised with IWB and outer membrane phosphoporin have a high survival rate with minimal damage to mice. This research proves outer membrane protein be used as a vaccine candidate (Hu et al, 2022).…”

Section: Discussionmentioning

confidence: 66%

Increased levels of IL-10 in the spleen after induction of pili protein 65.5 kDa Klebsiella pneumoniae

Agustina,

Diana Chusna Mufida,

Enny Suswati

et al. 2023

Pharm Educ

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Background: One of the gram-negative bacteria often found as the cause of nosocomial infections is Klebsiella pneumoniae. This bacterium has a mortality rate of 28.3% due to ESBL strains that cause resistance to several antibiotics and the absence of a vaccine as a preventive measure. Objective: To determine the level of IL-10 in the spleen after induction of the protein pili K. pneumoniae 65.5 kDa in mice. Method: This study used mice spleen samples from 21 mice aged six to eight weeks in an experimental investigation with a randomised posttest-only control group design. There are three groups, K1 as a PBS-given control, 65.5 kDa antigen protein pills + Freund’s adjuvants are given to K2, and Freund's adjuvants are given to K3. Interleukin-10 concentrations were measured using the ELISA and analysed by a one-way ANOVA assay. Result: The research showed significant differences in each group at IL-10 levels after administration of the pili protein K. pneumoniae using one-way ANOVA (p = 0.036). The treatment group had the highest average levels of IL-10, so there was an increased association between exposure to pili protein and IL-10 levels in rats. A significant increase in IL-10 levels was found in the treatment group compared to the control and adjuvant groups. Conclusion: Induction of protein pili Klebsiella pneumoniae 65.5 kDa increases IL-10 levels in spleen mice.

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Section: Discussionmentioning

confidence: 66%

Increased levels of IL-10 in the spleen after induction of pili protein 65.5 kDa Klebsiella pneumoniae

Agustina,

Diana Chusna Mufida,

Enny Suswati

et al. 2023

Pharm Educ

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“…This disproportionately impacted the pairwise reaction Jaccard distances (Figure 4B). Within published GSMMs, these transport reactions are catalysed by the non-specific porins OmpK35 (48,49), OmpK36 (50,51), OmpK37 (52,53) and phosphoporin PhoE (54,55), that simulate the generic transport of hydrophilic molecules into the cell when the specific enzymes are unknown.…”

Section: Resultsmentioning

confidence: 99%

A validated pangenome-scale metabolic model for theKlebsiella pneumoniaespecies complex

Cooper,

Vezina,

Hawkey

et al. 2023

Preprint

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TheKlebsiella pneumoniaeSpecies Complex (KpSC) is a major source of nosocomial infections globally with high rates of resistance to antimicrobials. Consequently, there is growing interest in understanding virulence factors and their association with cellular metabolic processes for developing novel anti-KpSC therapeutics. Phenotypic assays have revealed metabolic diversity within the KpSC, but metabolism research has been neglected due to experiments being difficult and cost-intensive.Genome-scale metabolic models (GSMMs) represent a rapid and scalablein silicoapproach for exploring metabolic diversity, which compiles genomic and biochemical data to reconstruct the metabolic network of an organism. Here we use a diverse collection of 507 KpSC isolates, including representatives of globally distributed clinically-relevant lineages, to construct the most comprehensive KpSC pan-metabolic model to-date, KpSC pan v2. Candidate metabolic reactions were identified using gene orthology to known metabolic genes, prior to manual curation via extensive literature and database searches. The final model comprised a total of 3,550 reactions, 2,403 genes and can simulate growth on 360 unique substrates. We used KpSC pan v2 as a reference to derive strain-specific GSMMs for all 507 KpSC isolates, and compared these to GSMMs generated using a prior KpSC pan-reference (KpSC pan v1) and two single-strain references. We show that KpSC pan v2 includes a greater proportion of accessory reactions (8.8%) than KpSC pan v1 (2.5%). GSMMs derived from KpSC pan v2 also result in more accuracy growth predictions than those derived from other references in both aerobic (median accuracy = 95.4%) and anaerobic (median accuracy = 78.8%). KpSC pan v2 also generates more accurate growth predictions, with high median accuracies of 95.4% (aerobic, n=37 isolates) and 78.8% (anaerobic, n=36 isolates) for 124 matched carbon substrates.KpSC pan v2 is freely available athttps://github.com/kelwyres/KpSC-pan-metabolic-model, representing a valuable resource for the scientific community, both as a source of curated metabolic information and as a reference to derive accurate strain-specific GSMMs. The latter can be used to investigate the relationship between KpSC metabolism and traits of interest, such as reservoirs, epidemiology, drug resistance or virulence, and ultimately to inform novel KpSC control strategies.Significance as a BioResource to the communityKlebsiella pneumoniaeand its close relatives in theK. pneumoniaeSpecies Complex (KpSC) are priority antimicrobial resistant pathogens that exhibit extensive genomic diversity. There is growing interest in understanding KpSC metabolism, and genome scale metabolic models (GSMMs) provide a rapid, scalable option for exploration of whole cell metabolism plus phenotype prediction. Here we present a KpSC pan-metabolic model representing the cellular metabolism of 507 diverse KpSC isolates. Our model is the largest and most comprehensive of its kind, comprising >2,400 genes associated with >3,500 metabolic reactions, plus manually curated evidence annotations. These data alone represent a key knowledge resource for theKlebsiellaresearch community; however, our model’s greatest impact lies in its potential for use as a reference from which highly accurate strain-specific GSMMs can be derived to inform in depth strain-specific and/or large-scale comparative analyses.Data summaryKlebsiella pneumoniaespecies complex (KpSC) pan v2 metabolic model available athttps://github.com/kelwyres/KpSC-pan-metabolic-model.All KpSC isolate whole genome sequences used in this work were reported previously and are available under Bioprojects PRJEB6891, PRJNA351909, PRJNA493667, PRJNA768294, PRJNA253462, PRJNA292902 and PRJNA391323. Individual accessions listed in Table S1.Strain-specific GSMMs used for comparative analyses (deposited in Figshare - 10.6084/m9.figshare.24871914), plus their associated MEMOTE reports (indicates completeness and annotation quality), reaction and gene presence-absence matrices across all isolates.Growth phenotype predictions derived from strain-specific GSMMs are available in Table S4.Binarised Biolog growth phenotype data for n=37 isolates (plates PM1 and PM2, aerobic and anaerobic conditions) are available in Tables S6 & S7.Additional growth assay data for six substrates not included on Biolog plates PM1 and PM2 (deposited in Figshare - 10.6084/m9.figshare.24871914).

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“…The complement-mediated antibacterial test was performed as previously described [ 36 , 37 ]. The pooled immunized or normal mice sera ( n = 5) were heat-inactivated in a 56 ℃ water bath for 1 h. A total of 10 6 bacterial cells ( K. pneumoniae strain NTUH-K2044 or ATCC 13,883) were co-incubated with 25% (v/v) human serum (providing the complement) donated by healthy volunteers with or without 5 µL heat-inactivated mice sera in a 50 µL reaction at 37 ℃ for 2 h. The colony count was calculated by the serial dilution method.…”

Section: Methodsmentioning

confidence: 99%

KbvR mutant of Klebsiella pneumoniae affects the synthesis of type 1 fimbriae and provides protection to mice as a live attenuated vaccine

Zhang

et al. 2022

Vet Res

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Klebsiella pneumoniae is a leading cause of severe infections in humans and animals, and the emergence of multidrug-resistant strains highlights the need to develop effective vaccines for preventing such infections. Live attenuated vaccines are attractive vaccine candidates available in the veterinary field. We recently characterized that the K. pneumoniae kbvR (Klebsiella biofilm and virulence regulator) mutant was a highly attenuated strain in the mice model. In the present study, the characterization, safety, and protective efficacy of ΔkbvR strain as a live attenuated vaccine were evaluated. The synthesis and activity of type 1 fimbriae were increased in the ΔkbvR strain. All mice inoculated by the subcutaneous route with 105, 106, and 107 colony-forming units (CFU) doses of the ΔkbvR strain survived. Subcutaneous immunization with two doses of 105 or 107 CFU ΔkbvR elicited a robust humoral immune response, and provided protection against the following K. pneumoniae intraperitoneal infection. The antisera of mice immunized with 105 CFU dose improved the opsonophagocytic ability and complement-mediated lysis not only to the same serotype strain but also to the different serotype strain. The passive transfer of antisera from 105 CFU dose-immunized mice provided protection against K. pneumoniae infection. Overall, our results suggest the great potential of the ΔkbvR strain as a novel vaccine candidate against K. pneumoniae infections in herds or humans.

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Immunogenic characteristics of the outer membrane phosphoporin as a vaccine candidate against Klebsiella pneumoniae

Cited by 9 publications

References 51 publications

Increased levels of IL-10 in the spleen after induction of pili protein 65.5 kDa Klebsiella pneumoniae

Increased levels of IL-10 in the spleen after induction of pili protein 65.5 kDa Klebsiella pneumoniae

A validated pangenome-scale metabolic model for theKlebsiella pneumoniaespecies complex

KbvR mutant of Klebsiella pneumoniae affects the synthesis of type 1 fimbriae and provides protection to mice as a live attenuated vaccine

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