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Published on: September 27, 2018
Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization
Eric Baranowski1, Dominique Bergonier2, Eveline Sagné2
1INRA, UMR 1225, IHAP, Toulouse, France; Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France.
Abstract:
Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.
Insights
The NIF locus is essential for Mycoplasma agalactiae to cause infection in sheep, as mutants lacking this gene cluster were unable to colonize or elicit an immune response, highlighting its role in pathogenesis.
Area of Science:
- Microbiology
- Infectious Diseases
- Veterinary Science
Background:
- Pathogenic mechanisms in Mycoplasma infections are not well understood due to limited similarity with known bacterial virulence factors.
- The NIF locus (including nifS and nifU) in Mycoplasma agalactiae was identified as crucial for in vitro growth but its in vivo significance was unknown.
Purpose of the Study:
- To evaluate the in vivo importance of the NIF locus in the pathogenesis of Mycoplasma agalactiae infections in its natural host.
Main Methods:
- Experimental infection of lactating ewes with the parental Mycoplasma agalactiae PG2 strain and two NIF locus knock-out mutants.
- Monitoring of systemic infection, colonization of body sites (lymph nodes, mammary gland), and host immune response (antibody production).
- Analysis of Mycoplasma agalactiae surface variable protein (Vpma) expression dynamics during infection.
Main Results:
- The parental PG2 strain successfully established systemic infection, colonizing various tissues and inducing a specific antibody response.
- Knock-out mutants of the NIF locus were completely avirulent, failing to survive or colonize the host, even at low inoculation doses.
- No IgG response was detected in animals inoculated with the NIF locus mutants, confirming their avirulent phenotype.
Conclusions:
- The NIF locus plays a critical role in the infectious process of Mycoplasma agalactiae in vivo.
- The NIF locus is likely essential for the pathogenesis of other pathogenic Mycoplasma species, as homologous genes are common.
- Further research is needed to elucidate the precise function of the NIF locus in Mycoplasma infections.
