Mycoplasma agalactiae Vpmas in host-pathogen interaction
Mycoplasma agalactiae Vpmas in host-pathogen interaction
Disciplines
Biology (60%); Veterinary Medicine (40%)
Keywords
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MYCOPLASMA AGALACTIAE,
VARIABLE SURFACE PROTEINS,
HOST PATHOGEN INTERACTIONS,
CONTAGIOUS AGALACTIA,
DNA REARRANGEMENTS,
RECOMBINASE
Research project P 14725 Mycoplasma agalactiae Vpmas in host-pathogen interactions Christine Citti 09.10.2000 The genus Mycoplasma contains over 100 species, several of which are known as classical pathogens and etiological agents of diseases in human and animals. Among mycoplasmas that induce mycoplasmosis in small ruminants, Mycoplasma agalactiae is the major etiological agent of Contagious Agalactia in sheep and goats. This disease is one of the most important mycoplasma diseases worldwide, characterized by mastitis, septicemia, arthritis, keratoconjonctivitis, as-well as sporadically occurring genital infections. Due to the lack of an effective antibiotic -therapy and, in particular, to the lack of effective vaccines and commercially available sensitive serodiagnostic tools, the economic losses caused by M. agalactiae in large dairy flocks and breeding systems present a significant problem in several countries. To date, M. agalactiae factors that promote colonization and induce host damages are not known. Recent investigations have identified in this agent a family of multiple but distinct, single-copy genes that undergo phase variation in expression via high-frequency DNA rearrangements within isogenic populations and that encode abundant surface proteins, designated Vpmas. The maintainance of such a large genetic system in an organism with a minute-size genome emphasizes the importance played by the associated gene products and raises the question of their function in the pathogenicity of the agent. The genetic and biochemical features of similar systems generating phase variation of multiple surface components have been deciphered in many other mycoplasma species, however little is known regarding their significance and their function in the host. Although a rapid alteration of its surface components would provide the wall-less mycoplasma with a means to avoid the host immune response, the exact role played by these variable sophisticated systems in optimizing the pathogen-host interactions and in the adaptation of the organism to the various complex niches encountered in the host during infection remain to be fully understand. The overall goal of this project is to define the exact genetic mechanism governing intraclonal variability of the Vpma surface components of M. agalactiae, its significance in the host-pathogen interaction, and the role played by the Vpmas in pathogenesis. Having recently cloned genes encoding six of these products, strategies include (i) to generate Vpma-specific serological reagents in order to identify individual Vpma products, (ii) to define the exact genetic mechanism underlying the phase variation of the vpma genes which is suspected to involve a site- specific recombinase for DNA rearrangements, (iii) to define the significance of Vpma oscillation in expression in animals infected with isogenic variants expressing defined Vpma phenotypes, (IV) to define the role of Vpmas in the decrease in milk production in infected animals, and (v) to define the host humoral response during infection. Reaching these aims is anticipated to provide information about the molecular basis of M. agalactiae pathogenesis and may also lead to valuable approaches for serodiagnosis and epidemiological assessment of M. agalactiae infections and for immunological intervention or prevention of Contagious Agalactia.
- Renate Rosengarten, Veterinärmedizinische Universität Wien , associated research partner
Research Output
- 136 Citations
- 3 Publications
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2008
Title Phase-locked mutants of Mycoplasma agalactiae: defining the molecular switch of high-frequency Vpma antigenic variation DOI 10.1111/j.1365-2958.2007.06103.x Type Journal Article Author Chopra-Dewasthaly R Journal Molecular Microbiology Pages 1196-1210 Link Publication -
2002
Title Surface Diversity in Mycoplasma agalactiae Is Driven by Site-Specific DNA Inversions within the vpma Multigene Locus DOI 10.1128/jb.184.21.5987-5998.2002 Type Journal Article Author Glew M Journal Journal of Bacteriology Pages 5987-5998 Link Publication -
2005
Title First steps towards the genetic manipulation of Mycoplasma agalactiae and Mycoplasma bovis using the transposon Tn4001mod DOI 10.1016/j.ijmm.2004.09.010 Type Journal Article Author Chopra-Dewasthaly R Journal International Journal of Medical Microbiology Pages 447-453 Link Publication