Mettenleiter, Thomas C.

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Strong together against infectionsScience • Society • IndustryZoonotic diseases - prevention and diagnostics The One Health ApproachProf. Dr. Dr. h.c. Thomas C. MettenleiterPresident of the Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health)Infect Control Board MemberSource: GIZOne HealthHumans are part of the animal kingdomin a shared environmentTwo Pillars of the One Health Concept- AMR – antimicrobial resistance- ZoonosesThe One Health Approach within Infect ControlMore than 30 research projects (interdisciplinary and transectoral)with more than 56 partners from science and industry.Diagnosis: BruCox (Pen-side-test Brucellosis and Q fever), RAPiD (Rodent-Associated Pathogen Chip-Detection), Life-Poc (Mobile Point-of-Care platform – Sepsis), Spot-LigHt (SPOT assays for high-risk bacterial strains)Vaccines: InVac (Tuberculosis), VacoME (S. pneumoniae, S. suis),Therapies: BTZ (Tuberculosis drug), MOASES (systemic effects of antimicrobial drugs), TTA (Transfer group Antiinfectives), DDP (Drug Development Project)AMR: Antires / Antires 2.0 (AMR spread in the environment),RAI-Projekt (rational use of antibiotics)© made by Lindgrün GmbH, 2014Based on the “One Health Concept” by Yvonne Agersø, EFFORT-project.One Health - RelevantTransmission Pathways and Risk Potential of multiresistentbacteria PetsHumansFruit, Vegetables,Feed plantsWildlifeFood-producinganimalsAnimal ProductsSociety PatientsANTIRES – Dissemination of antibiotic resistances in urban wastewaters Urban wastewater treatment plants: potential hot spots for AMRANTIRES – Dissemination of antibiotic resistances in urban wastewaters Urban wastewater treatment plants: potential hot spots for AMRANTIRES Urban wastewaters:• 16S rRNA marker gene analysis, metagenomics, metatranscriptomics, metaproteomics• hydrochemical analyses(nutrient availability, antibiotics)Comprehensive analysis of (antibiotic resistant) microbial community, expression of AMR genes/ proteins, and impact of environmental factorsCooperation with industrial partner: development of a rapid test for on-site rapid analysis of pollution with AMR genes ANTIRES 2.0 Application of plasma-based technologies to reduce the dissemination of AMR through urban wastewatersAntibiotics, potentially pathogenic, (multi)resistant bacteria:  present in all stages ofwastewater treatment, release into the environment with treated wastewatersAdditional treatments stages: essential to prevent dissemination of antibioticresistances through urban wastewatersMOASES – Meta-Omics-Analyses of systemic effects of antiinfective substancesWhich systemic effects are imposed by the two novelantiinfectives on the metabolism, the fitness & thepathophysiology of salmonellae and clostridiae in vitro? Salmonella entericaClostridium difficileDoes the application of the new antiinfectives result in an increased expression of resistance- or virulence-associated genes?Which impact do antibiotics have on the composition andfunctionality of the gut microbiota of piglets?Are there similarities / differences between the effects of thetwo novel antiinfectives in comparison to those of classicalantibiotics towards pathogens and commensals?Amido-chelocardinChlorotonil AMOASES – Meta-Omics-Analyses of systemic effects of antiinfective substancesANTIBIOTICS USAGEHuman medicine Veterinary medicine & agricultureModel PathogensSalmonella entericaClostridiumdifficileHuman-relatedPig-ModelFeed +/-Natural product / AB(META)-OMICS16S-rRNA-GEN-PROFILING (META)-TRANSCRIPTOMICSMETA-GENOMICSPROTEOMICSMETAPROTEOMICSData integrationData visualizationAntibiotics & antimicrobialnatural productsAmidochelocardinChlorotonil AErythromycinTetracyclinTwo Pillars of the One Health Concept- AMR – antimicrobial resistance- ZoonosesZoonoses: infectious diseases naturally transmitted between humans andother vertebrates (WHO 1959) https://www.oie.int/en/for-the-media/onehealth/The 13 most important (endemic) zoonoses account for 2.2 million deaths and 2.4 billion diseases each year. (Grace et al. 2012 Zoonoses Project 4, Report, ILRI)  manlivestockpet animalszoo animalswildlifeBovine Tuberculosis = Animal Tuberculosis = a multi-host infectious diseaseBarth, unpublished?InVac – Development of innovative vaccine against infections of the M. tuberculosis-complexfor use in veterinary and human medicineIntrabronchial inoculation (Mycobacterium caprae; BSL-3)15 x 0,5 mlEstablishment of a tuberculosis infection model in goatsIntrabronchial inoculation with M. bovis- Low dose group (n=4): 4.7 x 102 cfu- Medium dose group (n=4): 8.9 x 102 cfu- High dose group (n=4): 8.3 x 103 cfu- Control (n=4)InVac – Development of innovative vaccine against infections of the M. tuberculosis-complexfor use in veterinary and human medicineCourtesy S.H.E. Kaufmann, MPIIBConstruction of pro-apoptotic,pro-autophagic mutant (to enhance T cell responses)→ Deletion of nuoG from rBCG ΔureC-hly+Construction of safer rBCG(suitable for immuno-compromised newborns)→ Vitamin B6 auxotrophic strain (deletion of pdx from rBCG ΔureC-hly+)Bacterial-macrophage interplay of rBCG ΔureC-hly+(vaccine strain VPM 1002)DIVA = Differentiating infected from vaccinated animalsInVac – Development of innovative vaccine against infections of the M. tuberculosis-complexfor use in veterinary and human medicineBruCox: Save Diagnostics as Prevention Strategy of Zoonotic Agents Goal: Development of Pen-side-test for on site detection of Brucellosis and Q fever – zoonotic  diseases with high economic and public health impact.Strategy: Pathogen Detection → Reservoir Elimina on → Disease Control Identification andproduction of bacterialimmunoreactive proteinsDevelopment and production of antigen detection assaysDevelopment of detectionassays for Pen-side-test (PST) devicesBruCox: Save Diagnostics as Prevention Strategy of Zoonotic Agents Results:• Coxiella burnetii outer membrane protein 1 (Com1) ELISA assay for detectionof C. burnetii-specific antibodies from ruminant serum samples(Sensitivity 77%; Specificity 72%)• Generation and selection of antibodies directedagainst viable C. burnetii Phase I and Phase II for on site antigen detection. Antigens  Coxiella-specific antigens and antibodiesare the foundation for the development ofon site / pen site detection tools.Pathogen / Reservoir detection→ Control and preventionmouse anti-C. burnetiiExample: SARS-CoV-2• Zoo-Anthroponotic Spill-over most likelyfrom horseshoe bats in Southern China tohumans (contact animal-human). Unclear when, where and how.• High Human Population Density results in selection for efficient human-to-human transmission• Global Mobility leads to pandemic spread• Anthropo-Zoonotic Transmission to kept animals• Zoo-Anthroponotic Transmission to attending humansN. Engl J Med 373;2 nejm.org July 9, 2015https://doi.org/10.1056/NEJMoa1415627www.fotocommunity.com08 October 2020Nature 586, 424–428 (2020). https://doi.org/10.1038/s41586-020-2812-9RAPiD –Rodent-Associated Pathogen Chip-Detection On-Site-Plattform for the rapid DNA-based detection of importantbacterial and viral zoonotic pathogens in humans and animalsApplications: Monitoring and Screening bed-side- / pen-side Diagnosticof rodent populations of zoonotic infections inin high risk regions humans and animalsPathogen monitoring using an open source system(extentable to other pathogens and/or AMR-genes)RAPiD –Rodent-Associated Pathogen Chip-Detection Proof of principle of the plasmonic microarray:Probes of Leptospira spp., Coxiella burnetii, Puumala-Orthohantavirus(PUUV), Orthopoxvirus (OPV) and Variegated Squirrel Bornavirus (VSBV-1)RAPiD-Demonstrator in ActionThank you for your attention

Zoonotic Diseases - prevention and diagnostics : The One Health Approach

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Zoonotic Diseases - prevention and diagnostics : The One Health Approach

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