Stress-induced mutagenesis in bacteria

Abstract

Bacteria spend their lives buffeted by changing environmental conditions. To adapt to and survive these stresses, bacteria have global response systems that result in sweeping changes in gene expression and cellular metabolism. These responses are controlled by master regulators, which include: alternative sigma factors, such as RpoS and RpoH; small molecule effectors, such as ppGpp; gene repressors such as LexA; and, inorganic molecules, such as polyphosphate. The response pathways extensively overlap and are induced to various extents by the same environmental stresses. These stresses include nutritional deprivation, DNA damage, temperature shift, and exposure to antibiotics. All of these global stress responses include functions that can increase genetic variability. In particular, up-regulation and activation of error-prone DNA polymerases, down-regulation of error-correcting enzymes, and movement of mobile genetic elements are common features of several stress responses. The result is that under a variety of stressful conditions, bacteria are induced for genetic change. This transient mutator state may be important for adaptive evolution.

FIGURE 1

The accumulation of Lac⁺ mutations in liquid minimum lactose medium. Eight independent cultures of FC40 were diluted into minimum lactose medium and 100 μl aliquots containing approximately 10⁶ cells were dispensed into 726 microtiter dish wells. Turbid wells were counted daily. The total number of Lac⁻ cells was determined in cultures incubated in parallel. The minimum lactose medium had been scavenged of non-lactose carbon sources by incubating it with 10⁹ Δ(lac) cells per mL for three hours; these cells were removed by centrifugation followed by filtration. Because it takes 2 days for a well to become turbid after a Lac⁺ mutation occurs, the mutations per well have been shifted two days to the left. (Reprinted with permission from Foster, 1994. Genetics. 138:256. The Genetics Society of America. www.genetics.org.)

FIGURE 2

A model for recombination-dependent mutation. A and B: the replication fork initiated at oriS collapses when it encounters the nick at oriT, creating a double-strand end. C and D: RecA and RecBCD catalyze invasion of the broken arm into the homologous region of the sister chromosome or a different episome copy. E: the PriA-primosome initiates DNA synthesis from the invading 3′ end, using either Pol IV or Pol II; the four-stranded Holliday junction is formed. F: the replication fork is re-established with Pol III. Not shown: the Holliday junction is resolved by RuvABC. Dashed lines are newly synthesized DNA; dotted lines are DNA synthesized after recombination. The arrow head indicates the 3′ end of the leading DNA strand; ^* at oriT indicates TraI. (Reprinted, with permission, from Foster 1999, Ann Rev Gene 33:62. Annual Reviews. www.annualreviews.org)

FIGURE 3

The relationship between the proportion of Lac⁺ revertants that occur in the hypermutating subpopulation (Y axis), the proportion of cells that are hypermutators (X axis), and the elevation in mutation rate in the hypermutating cells (M). The curves are base on the derivation by Cairns (1998).