Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.
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.
INRA, UMR 1225, IHAP, Toulouse, France; Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France.
Eric
E
Baranowski
Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France; INRA, UMR 1225, IHAP, Toulouse, France.
Dominique
D
Bergonier
Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France; INRA, UMR 1225, IHAP, Toulouse, France.
Eveline
E
Sagné
INRA, UMR 1225, IHAP, Toulouse, France; Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France.
Marie-Claude
MC
Hygonenq
Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France.
Patricia
P
Ronsin
Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France; INRA, UMR 1225, IHAP, Toulouse, France.
Xavier
X
Berthelot
INRA, UMR 1225, IHAP, Toulouse, France; Université de Toulouse, INP-ENVT, UMR 1225, IHAP, Toulouse, France.
Christine
C
Citti
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056426:Genetic Loci; D054884:Host-Pathogen Interactions; D009154:Mutation; D009175:Mycoplasma Infections / Q000382:microbiology / Q000662:veterinary*; D045644:Mycoplasma agalactiae / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D012756:Sheep / Q000382:microbiology*; D012757:Sheep Diseases / Q000382:microbiology*
D001426:Bacterial Proteins