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One of the most important pathogenic mycoplasma species in sheep and goats, Mycoplasma agalactiae, has been the subject of research at the Institute of Microbiology, formerly the Institute of Bacteriology, Mycology and Hygiene, at Vetmeduni Vienna for many years. By specifically inactivating a certain area in the genome of this pathogen the researchers made an important step forward, especially due to the fact that mycoplasmas are generally difficult to manipulate genetically. They were able to use these so-called knock-out mutants to explore for the first time those mechanisms used by the mycoplasmas to outsmart the immune defences during an infection in a natural host organism. The mycoplasmas were found to be such clever "genomic strategists" that they could even compensate for the artificial gene inactivation.
"We have known for several years that some mycoplasma species possess gene families that produce highly variable proteins for the membrane surface. These proteins compensate for the lack of a cell wall, but they are recognized by the immune system as antigens, thus foreign proteins," explains first author Rohini Chopra-Dewasthaly. The genes are therefore subject to phase variation, which means that they can be spontaneously switched on and off at high frequency and be replaced by other variants. Through this surface variation the mycoplasmas are equipped with a sort of molecular stealth mechanism that can outsmart the immune system.
Researchers - Vetmeduni - Vienna - Component - Mechanism
The researchers from Vetmeduni Vienna identified an important component of this mechanism, an enzyme called recombinase, and were able to deactivate it through genetic modification. "This stopped the phase variation so that the surface of the mycoplasmas could no longer change," says senior author Renate Rosengarten. The laboratory-produced mycoplasmas, called phase-locked mutants, were tested for the first time in vivo, namely in sheep,...
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