Homeostasis is the ability of an organism to stabilise its internal body metabolism in response to changes in the external environment. The ability to carry out homeostasis provides an organism a lot of freedom from the dependence on the external environment. For example, reptiles are cold blooded animals. They require the heat of the sun for body metabolism. But in the absence of heat or in case of harsh winters, the reptiles will not be able to adjust to the temperature and as a result perish. Mammals are warm-blooded animals, being able to regulate their internal body temperature as and when necessary. Winters will affect the warm-blooded animals less because their body will increase in metabolism in response to cold temperatures to raise the internal body temperature. This is possible only through homeostasis.
When directed mutagenesis which is also called reverse genetics is used, only a single mutation per genome is introduced. In contrast, the number of mutations per genome introduced by random mutagenesis is usually difficult to control. It is likely that the strain you obtained with a mutation in gene X after random mutagenesis contained an additional mutation or perhaps multiple mutations which ultimately was/were responsible for loss of virulence in your favorite pathogen.