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03/11/2021

Joint Research Unit on Animal mycoplasmas of the Lyon Laboratory

UMR Director: Claire Becker (VetAgro Sup)

Deputy Director and Head of Unit: Fabien Labroussaa

Created in April 2004, under the supervision of VetAgro Sup and ANSES, the Joint Research Unit on Animal mycoplasmas (MYCO UMR) specialises in the study of Mycoplasma, a bacterial genus responsible for several animal diseases. It employs a workforce of 14 people, including nine permanent scientists, with two PhD students and one to three university students per year on average.

The missions of the MYCO UMR involve research and training through research in the area of mycoplasmology in animals, with historical expertise relating to ruminant mycoplasmas. These are combined with ANSES's expert appraisal and reference missions and the education missions of VetAgro Sup. The UMR carries out scientific work evaluating the biodiversity of bacteria of the genus Mycoplasma and the clinical expression of related diseases.

The UMR is a member of the educational and guidance committee of the Evolution, Ecosystems, Microbiology & Modelling Doctoral School of University of Lyon (E2M2). It is also a member of the European Mycoplasma Research Network eMyNet.

Surveillance activities

The UMR coordinates the Vigimyc network on ruminant mycoplasmas. In addition to carrying out missions involving epidemiological surveillance and monitoring with regard to exotic mycoplasmas, and diagnostic support for veterinary analytical laboratories, the network maintains a collection of mycoplasma strains used in multiple research projects.

Research activities

The research projects of the MYCO UMR mainly focus on the diversity and antimicrobial resistance of animal mycoplasmas and on their virulence and emergence.

The unit’s research activities are for the most part finalised, with the aim of establishing structural links between clinical observations (outcome of diseases, therapeutic uses, economic impact and epidemiological surveillance) and the characterisation of pathogens (identification, genetic polymorphism, antimicrobial resistance, virulence). Close relations between the MYCO UMR and production sectors, diagnostic laboratories, veterinary practitioners and professional health organisations ensure that their research activities provide real benefits in the area of animal health.

The most fundamental research projects are usually carried out in collaboration with university partners and research organisations, in particular through the joint supervision of PhD theses.

Since 2020, under a partnership with INRAE, the MYCO UMR has been jointly developing cell model expertise to study the pathophysiology of mycoplasma infections. In the medium term, these models will be used to study antimicrobial resistance in conditions closer to those of the living world. Similarly, with the development of projects based on high-throughput sequencing, there are plans to link a genomic surveillance system (detection of atypical strains, definition of species or virulence markers, monitoring of these markers over time, etc.) to the Vigimyc epidemiological surveillance network.

Main research projects, from the last five years and ongoing

MYCOPAB (2020-2023)

Mycoplasmas in respiratory infections in horses: the species involved, their prevalence and their antimicrobial resistance

Funding: French Horse and Riding Institute, Eperon Fund, Centaure scientific interest group, including a doctoral thesis

Partner: LABÉO testing and research centre in Normandy

The Mycopab project has three interconnected objectives: develop tools to identify equine mycoplasmas in the respiratory tract as well as detection tools – quantitative if possible – for the evaluation of prevalence and for routine diagnostic purposes; determine the antimicrobial resistance profiles of isolated strains and the underlying molecular mechanisms; and engage in comparative epidemiology, distinguishing between mycoplasma species involved in disease or poor sporting performance and species not responsible for any symptoms.

MYCO3D_LUNG (2020-2023)

Respiratory mycoplasma infection, role of the resident microbiota and chemotherapy control: what could we learn using different respiratory epithelium models in vitro

Funding: FINOVI Infectiology Foundation

Partner: Viral Infections and Comparative Pathology UMR (EPHE higher education and research institution/INRAE/University of Lyon)

This project is using various cell models (from the simplest to the most complex: cell lines, epithelia at the air-liquid interface, organoids) to understand the pathophysiology of respiratory infections with M. bovis. The processes by which mycoplasmas adhere to and invade cells are studied, as is the cellular response to these infections, with or without co-infection and/or antibiotics.

ADAPT-MYCO (2020-2021)

Comparative genomic epidemiology of two (sub)species of pathogenic ruminant mycoplasmas

Funding: SAARA network (thematic research network for animal health and welfare in the Auvergne-Rhône-Alpes region)

Partner: Epidemiology of Animal and Zoonotic Diseases UMR (INRAE/VetAgro Sup)

This genomic epidemiology project consists in exploring the evolution and diversity over time of populations of two (sub)species of mycoplasmas, M. bovis and M. mycoides subsp. capri, which have evolved very differently in terms of antimicrobial resistance and diversity. Analysis of around 100 genomes of each sub-species, corresponding to isolates spread out over time and through space, will provide knowledge on the spread of these bacteria and their adaptation to the circulation conditions imposed by the zootechnical and health management practices implemented on the farms they impact.

REDIBOV (2018-2020)

Monitoring of trends in diversity and loss of antimicrobial susceptibility in M. bovis, a major pathogen for bronchopneumonia in calves: ecology, risk factors and health consequences.

Funding: Directorate General for Food, as part of the EcoAntibio2 plan

In partnership with sector professionals, field collection campaigns were carried out to isolate Mycoplasma bovis strains from calves during the fattening process. Their health contexts were known and controlled: sick or healthy animals, before or after antibiotic treatment. Characterisation of the isolates demonstrated that the antibiotic treatments had no impact on the genetic diversity or antimicrobial resistance of the M. bovis strains from calves. Moreover, an analysis of risk factors showed that the spread of M. bovis infection, estimated by serology, was greater on large farms with automatic milk feeders.

MAGA_R (2015-2018)

Mechanisms of emerging in vitro antimicrobial resistance in M. agalactiae: a model for ruminant mycoplasmas

Funding: Thesis funded jointly by the National Veterinary School of Toulouse (ENVT) and ANSES

Partners: Host-Pathogen Interactions UMR (INRAE, ENVT)

This project explored the role of unconventional horizontal transfers of chromosomal regions via conjugation (mycoplasma chromosomal transfer (MCT)) in the acquisition of antimicrobial resistance in the model species Mycoplasma agalactiae. A number of spontaneously resistant mutants and transconjugants selected for their resistance were sequenced. The results showed that in vitro, MCT led to the simultaneous transfer of multiple fragments, generating a varied population of mycoplasmas with highly mosaic genomes. This could contribute to accelerating the spread of antimicrobial resistance via the simultaneous acquisition of several distant mutations associated with resistance.

EXOVIR (2021-2024)

The secretome of animal mycoplasmas: inter-species comparison, role in pathogenicity and application to diagnostics

Funding: ANSES, Saint-Brieuc urban community and Côtes-d'Armor Departmental Council

Thesis project currently being signed

Partners: MBA Unit of ANSES's Ploufragan-Plouzané-Niort Laboratory

Prior work demonstrated that despite their apparent simplicity, mycoplasmas have a complex (capsular polysaccharides and exopolysaccharides, exoproteins, extracellular vesicles) secretome (all of the components secreted at the surface of bacteria or released into the environment) that undoubtedly plays a major role in interactions with hosts. The Exovir project aims to supplement the descriptive data on the secretome in ruminant mycoplasmas, broadened to other animal hosts. The universality of certain components will enable an “all mycoplasmas” approach to virulence to be used, targeting markers of virulence in the secretome found regardless of the mycoplasmal species; in the longer term, the usefulness of certain elements of the secretome for vaccination strategies may be considered.

MyMIC (2023-2025)

Partners: 15 European countries and three third countries are involved in this collaboration, a total of 50 scientists

Funding: French Research Agency (ANR)

MyMIC is a European networking project funded by the ANR as part of the Joint Programming Initiative on Antimicrobial Resistance (JPI-AMR) call for projects. It aims to build a network for exchanging good practice and harmonising methodologies in the diagnosis and determination of antimicrobial resistance in animal mycoplasmas of veterinary interest.

DIAMS (2023-2025)

Feasibility of determination during diagnosis of antimicrobial resistance in ruminant mycoplasmas.

Funding: Directorate General for Food, as part of the EcoAntibio plan

Partners: LABOCEA35 (cattle), Aveyron Labo (sheep), Qualyse (goats).  

Rapid phenotypic methods for assessing antimicrobial resistance (antibiograms or E-tests) are not applicable to mycoplasmas. ANSES uses the determination of minimum inhibitory concentrations (MICs) by dilution in agar medium as part of the Vigimyc network's surveillance activities. This technique is cumbersome, cannot be automated and is unsuitable for analysis during diagnosis. This project aims to:

-develop, optimise and validate the performance and robustness of MIC determination by microdilution in a format compatible with the routine operations of veterinary diagnostic laboratories (VDLs).

- review the latest developments in molecular and/or genomic methods for assessing the antimicrobial resistance of mycoplasmas, and assess the feasibility of deploying these methods in VDLs.

MYTROUC (2021-2024)

Assessment of the role of vaginal mycoplasmas in reproductive disorders in female dogs

Partners: Neocare team (ENVT, funding body), CERREC (VetAgro Sup) and in the longer term the other French national veterinary schools

Since 2020, the UMR has broadened its scientific themes to include species of pathogenic mycoplasmas in animals, excluding pigs and poultry, covered by the Ploufragan-Plouzané-Niort laboratory. The project consists in determining the involvement of mycoplasmas in reproductive disorders in female dogs (pregnancy failure and puppy mortality), with identification of the mycoplasma species present and the correlation between the presence/abundance of these species and the clinical status of the animal. Tools need to be developed to study the species present, using non-targeted bioinformatics analyses. Sampling is initially being carried out on dogs coming for consultations in the partner veterinary schools. The project will then be extended to the other two French national veterinary schools. In the longer term, analyses will be carried out to determine the antimicrobial resistance of the isolated mycoplasmas.