Application of TonB-Dependent Transporters in Vaccine Development of Gram-Negative Bacteria

Jia, Weiping; Xiong, Kun; Pan, Qu; He, Weifeng; Cong, Yanguang

doi:10.3389/fcimb.2020.589115

Cited by 22 publications

(21 citation statements)

References 84 publications

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“…Inactivation of fur was expected to result in the constitutive production of iron-limitation-inducible receptors in the OM, which are potentially relevant vaccine antigens (Wang et al . 2021 ). So far, 12 and 16 putative TonB-dependent receptors have been identified in B. pertussis and B. bronchiseptica , respectively (Brickman et al .…”

Section: Discussionmentioning

confidence: 99%

“…TonB-dependent receptors are considered attractive vaccine candidates, since they are exposed at the cell surface, upregulated in vivo , and essential for successful infection (Wang et al . 2021 ). Besides, iron limitation also leads to increased expression of other vaccine candidates, such as IRP1-3 and the type III secretion system in Bordetella (Alvarez Hayes et al .…”

Section: Introductionmentioning

confidence: 99%

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Conditional growth defect of Bordetella pertussis and Bordetella bronchiseptica ferric uptake regulator (fur) mutants

Jonge

Tommassen

2022

FEMS Microbiology Letters

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Outer-membrane vesicles (OMVs) are promising tools in the development of novel vaccines against the respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica. Unfortunately, vesiculation by bordetellae is too low for cost-effective vaccine production. In other bacteria, iron limitation or inactivation of the fur gene has been shown to increase OMV production, presumably by downregulation of the mla genes, which encode machinery for maintenance of lipid asymmetry in the outer membrane. Here, we followed a similar approach in bordetellae. Whereas a fur mutant was readily obtained in B. bronchiseptica, a B. pertussis fur mutant could only be obtained in iron-deplete conditions, indicating that a fur mutation is conditionally lethal in this bacterium. The fur mutants displayed a growth defect in iron-replete media, presumably because constitutive expression of iron-uptake systems resulted in iron intoxication. Accordingly, expression of the Escherichia coli ferritin FtnA to sequester intracellularly accumulated iron rescued the growth of the mutants in these media. The fur mutations led to the constitutive expression of novel vaccine candidates, such as the TonB-dependent receptors FauA for the siderophore alcaligin and BhuR for heme. However, neither inactivation of fur nor growth under iron limitation improved vesiculation, presumably because the expression of the mla genes appeared unaffected.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conditional growth defect of Bordetella pertussis and Bordetella bronchiseptica ferric uptake regulator (fur) mutants

Jonge

Tommassen

2022

FEMS Microbiology Letters

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“…TonB-dependent receptors contribute to the transport and nutrient absorption [90]. Recently, they have been the subject of research for developing vaccines against Gram-negative bacteria because of their cell multiple functions [92–93].…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Comparative Genomic revels: Bacteroides fragilis is a reservoir of antibiotic resistance genes in the gut microbiota

Evanovich

Mattos

Guerreiro

2022

Preprint

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Bacteroides fragilis are commensal bacteria of the gut microbiota of mammals and may cause severe infection in a susceptible host. Treatment can be cumbersome if multidrug resistant strains are present in the affected tissue. The principal aim of this study was to provide new insights into the genomic properties of B. fragilis through different approaches in comparative genomics. Results revealed that the pan-genome is opened, and an intense exchange of genetic material reinforces this inference. The Don complex, responsible for extraintestinal adaptation, is present in all strains, suggesting a crucial role for B. fragilis adaptation. CRISPR-Cas system is at 76% of the samples, but it apparently has low accuracy against prophage. Multidrug resistance genes are in 80% of strains. Conjugative transposons and integrative and conjugative elements (ICE) are the main spreaders of genes for antimicrobial resistance. We also reported evidence for horizontal gene transfer (HGT) of antimicrobial resistance genes among the B. fragilis strains and Bacteriodales. At least 398 genes are under positive selection, including genes for antimicrobial resistance and transport of toxins and nutrients.

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“…TonB-dependent siderophore receptor mediates the transport of siderophores into the periplasm in Gram-negative bacteria [ 91 ]. Other iron-related antigens identified though not common across all strains studied here, include the siderophore amonabactin TonB-dependent receptor and TonB-dependent hemoglobin/transferrin/lactoferrin.…”

Section: Discussionmentioning

confidence: 99%

Comparative Reverse Vaccinology of Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella viscosa, Frequent Pathogens of Atlantic Salmon and Lumpfish Aquaculture

et al. 2022

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Marine finfish aquaculture is affected by diverse infectious diseases, and they commonly occur as co-infection. Some of the most frequent and prevalent Gram-negative bacterial pathogens of the finfish aquaculture include Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella viscosa. To prevent co-infections in aquaculture, polyvalent or universal vaccines would be ideal. Commercial polyvalent vaccines against some of these pathogens are based on whole inactivated microbes and their efficacy is controversial. Identification of common antigens can contribute to the development of effective universal or polyvalent vaccines. In this study, we identified common and unique antigens of P. salmonis, A. salmonicida, Y. ruckeri, V. anguillarum and M. viscosa based on a reverse vaccinology pipeline. We screened the proteome of several strains using complete available genomes and identified a total of 154 potential antigens, 74 of these identified antigens corresponded to secreted proteins, and 80 corresponded to exposed outer membrane proteins (OMPs). Further analysis revealed the outer membrane antigens TonB-dependent siderophore receptor, OMP assembly factor BamA, the LPS assembly protein LptD and secreted antigens flagellar hook assembly protein FlgD and flagellar basal body rod protein FlgG are present in all pathogens used in this study. Sequence and structural alignment of these antigens showed relatively low percentage sequence identity but good structural homology. Common domains harboring several B-cells and T-cell epitopes binding to major histocompatibility (MHC) class I and II were identified. Selected peptides were evaluated for docking with Atlantic salmon (Salmo salar) and Lumpfish MHC class II. Interaction of common peptide-MHC class II showed good in-silico binding affinities and dissociation constants between −10.3 to −6.5 kcal mol−1 and 5.10 × 10−9 to 9.4 × 10−6 M. This study provided the first list of antigens that can be used for the development of polyvalent or universal vaccines against these Gram-negative bacterial pathogens affecting finfish aquaculture.

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Application of TonB-Dependent Transporters in Vaccine Development of Gram-Negative Bacteria

Cited by 22 publications

References 84 publications

Conditional growth defect of Bordetella pertussis and Bordetella bronchiseptica ferric uptake regulator (fur) mutants

Conditional growth defect of Bordetella pertussis and Bordetella bronchiseptica ferric uptake regulator (fur) mutants

Comprehensive Comparative Genomic revels: Bacteroides fragilis is a reservoir of antibiotic resistance genes in the gut microbiota

Comparative Reverse Vaccinology of Piscirickettsia salmonis, Aeromonas salmonicida, Yersinia ruckeri, Vibrio anguillarum and Moritella viscosa, Frequent Pathogens of Atlantic Salmon and Lumpfish Aquaculture

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