Genome (in)stability in bacteria

Bacteria can adapt to environmental changes by adjusting gene expression, by controlling protein activity, or by accumulation of beneficial mutations. The accumulation of mutations can be detrimental for the bacteria. However, it is often the last option to ensure survival in a specific environment. B. subtilis mutant strains lacking the key enzymes involved in glutamate metabolism have a growth defect (Fig. A). For instance, a strain lacking a functional glutamate dehydrogenase (GDH) rapidly activates a second GDH that is inactive in common laboratory strains (Fig. B). The suppressor mutants have always excised one part of a perfect direct repeat that is present in the cryptic gdh^CR gene and renders the encoded GDH inactive (Fig. C). Moreover, the glutamate auxotrophy of a strain lacking the glutamate synthase genes can be relieved by diverse mutations, illustrating a flexible genome. We are currently working on the identification of novel factors that affect the (in)stability of the B. subtilis genome (Fig. D). Elucidating the underlying molecular mechanisms crucial for genome maintenance and adaptability is important for understanding the basic principles of molecular evolution. Moreover, the removal of factors causing genome instability may help to engineer stable production strains for industrial applications.

Figures. (A) Lack of GDH activity (here RocG) affects physiology of the cell. (B) A functional GDH is important for growth of B. subtilis on rich medium and the bacteria rapidly acquire suppressor mutations. (C) A mutant strain lacking RocG activates the second GDH GudB. (D) Transcription is important for mutagenesis of the cryptic gudB^CR gene.

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