Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

Thibau, Arno; Dichter, Alexander A.; Vaca, Diana J.; Linke, Dirk; Goldman, Adrian; Kempf, Volkhard A. J.

doi:10.1007/s00430-019-00649-y

Cited by 16 publications

(13 citation statements)

References 249 publications

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“…17,18 In our study, ). 19 TAAs of B bacilliformis were already considered as potential vaccine targets due to their homology to Neisseria meningitidis NadA, which is included in the Bexsero meningococcal group B vaccine (GlaxoSmithKline, Brentford, UK). 10,11 However, the reactivity of BbadA and BbadB with approximately 10% of the control serum samples excludes their potential use as specific immunoreactive proteins.…”

Section: Discussionmentioning

confidence: 99%

Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach

et al. 2021

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Background Bartonella bacilliformis is the aetiological agent of Carrión's disease, a biphasic and highly lethal illness formerly restricted to the South American Andes that is now spreading to adjacent areas. Reliable serodiagnostic approaches and vaccines are urgently needed. In this study, we aimed to identify immunodominant proteins of B bacilliformis and to establish novel and reliable serodiagnostic tools. MethodsWe used a reverse vaccinology approach in combination with an analysis of heterologous genomic expression libraries to identify immunodominant proteins, on the basis of the genome sequences of B bacilliformis strains KC583 and KC584. Antigens were screened with serum samples collected from Peruvian patients with B bacilliformis infections and from German healthy blood donors without history of travel to South America. We further analysed immunoreactive proteins of B bacilliformis with immunoblotting and line blots. We used selected target proteins to develop a diagnostic ELISA. To assess the performance of this ELISA, we did receiver operating characteristic analyses to assess the area under the curve, cutoff values, sensitivities, and specificities with 95% CIs. FindingsWe used serum samples obtained between Dec 23, 1990, and May 5, 2018, from 26 Peruvian patients with B bacilliformis infections and serum samples taken between Aug 28 and Aug 31, 2020, from 96 healthy German blood donors. 21 potentially immunodominant proteins were identified and recombinantly expressed, and their reactivity was assessed with immunoblotting and line blots. Of these 21 antigens, 14 were found to be immunoreactive. By using serum samples of Peruvian patients with Carrión's disease and of healthy German blood donors, we identified three antigens (porin B, autotransporter E, and hypothetical protein B) as suitable immunodominant antigens, and we applied them in a diagnostic ELISA using two different antigen combinations (porin B plus autotransporter E and porin B plus autotransporter E plus hypothetical protein B). For the combination of porin B and autotransporter E, with optical density measured at 450 nm (OD 450 ) cutoff value of 0•29, sensitivity was 80•8% (95% CI 60•7-93•5) and specificity was 94•8% (88•3-98•3) for all Peruvian patient samples. For a combination of porin B, autotransporter E, and hypothetical protein B, with an OD 450 cutoff of 0•34, sensitivity was 76•9% (56•4-91•0) and specificity was 93•8% (86•9-97•7) for all Peruvian patient samples. Interpretation This novel ELISA could represent a useful serodiagnostic tool for future epidemiological studies of B bacilliformis in endemic areas. Additionally, the immunodominant antigens we have identified could provide a first basis for future vaccine development to prevent the highly lethal Carrión's disease. Funding DRUID (Novel Drug Targets against Poverty-Related and Neglected Tropical Infectious Diseases) Initiative and Robert Koch Institute.

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Section: Discussionmentioning

confidence: 99%

Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach

et al. 2021

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“…TAAs have been considered as potential candidates for the development of vaccines in several microorganisms, including members of the Bartonella genus [46]. The present analysis showed two members of this family: Vomp and YadA-like.…”

Section: Discussionmentioning

confidence: 57%

In-silico identification of potential antigenic proteins in Bartonella bacilliformis for the serological diagnosis of Carrions’ disease

Jiménez-Vásquez

Calvay-Sanchez

Zarate-Sulca

et al. 2022

Preprint

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The current methods for inferring antigenic, pathogenic or virulence factors in bacteria include in-silico or computational tools. Bartonella bacilliformis, the causal agent of Carrion's disease (CD) is a Gram-negative microorganism transmitted by the sand fly Lutzomya verrucarum mainly in Peruvian Inter-Andean valleys. A better understanding of the pathogenicity of B. bacilliformis, the implementation of serological diagnostic methods and the development of candidate vaccines for the control of CD could be facilitated by the identification of outer membrane exposed proteins such as outer-membrane beta-barrels (OMBB) and outer-membrane lipoproteins (OMLPP). In this study we present the in-silico identification of OMBBs and OMLPPs in B. bacilliformis. The present analysis identified 32 OMBBs and 9 OMLPPs, of which 15 and 4 are reported for the first time as potential antigenic, pathogenic and virulence-related proteins, respectively. Future implications of this study are discussed and compared with proteins validated by experimental assays.

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“…In many Gram-negative bacteria trimeric autotransporter adhesins enable bacterial adhesion to extracellular matrix, also to epithelial cells, and were recently investigated for A. baumannii (Ata protein), Brucella spp., B. cenocepacia , and H. influenzae (Hia proteins) [6 ▪ ,7 ▪ ,8]. They are in the focus of recent research since, besides adhesion and invasion, they are immunogenic and thus, currently reviewed as potential vaccine candidates [31]. Not only bacterial proteins covalently or noncovalently attached to the bacterial surface are able to mediate host matrix binding.…”

Section: Adhesion and Invasion As Critical Steps To Cause Intracellul...mentioning

confidence: 99%

The intracellular phase of extracellular respiratory tract bacterial pathogens and its role on pathogen-host interactions during infection

Lamberti

Surmann

2021

Current Opinion in Infectious Diseases

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Purpose of review An initial intracellular phase of usually extracellular bacterial pathogens displays an important strategy to hide from the host's immune system and antibiotics therapy. It helps the bacteria, including bacterial pathogens of airway diseases, to persist and eventually switch to a typical extracellular infection. Several infectious diseases of the lung are life-threatening and their control is impeded by intracellular persistence of pathogens. Thus, molecular adaptations of the pathogens to this niche but also the host's response and potential targets to interfere are of relevance. Here we discuss examples of historically considered extracellular pathogens of the respiratory airway where the intracellular survival and proliferation is well documented, including infections by Staphylococcus aureus, Bordetella pertussis, Haemophilus influenzae, Pseudomonas aeruginosa, and others. Recent findings Current studies focus on bacterial factors contributing to adhesion, iron acquisition, and intracellular survival as well as ways to target them for combatting the bacterial infections. Summary The investigation of common and specific mechanisms of pathogenesis and persistence of these bacteria in the host may contribute to future investigations and identifications of relevant factors and/or bacterial mechanisms to be blocked to treat or improve prevention strategies.

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Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

Cited by 16 publications

References 249 publications

Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach

Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach

In-silico identification of potential antigenic proteins in Bartonella bacilliformis for the serological diagnosis of Carrions’ disease

The intracellular phase of extracellular respiratory tract bacterial pathogens and its role on pathogen-host interactions during infection

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