A mutation in a new gene of Escherichia coli, psu, requires secondary mutations for survival: psu mutants express a pleiotropic suppressor phenotype.

A mutation in an apparently new gene of Escherichia coli, psu, maps close to ara (1.3 min). psu mutants express a pleiotropic suppressor phenotype in which several auxotrophic requirements and some deletion mutations are suppressed. psu cloned in pBR322 can be maintained by the transformed cell only in the presence of several secondary mutations which accumulate in cultures of psu mutants and have an apparently compensatory role. The accumulation of secondary mutations is not due to mutator activity. The secondary mutations can each act as a suppressor of an auxotrophic requirement in the absence of psu, while suppression of deletions requires the presence of psu. Thus, the suppressor phenotype of psu mutants is due to both psu and the secondary mutations. The functions of psu and the secondary mutations are not known. However, two observations suggest an association with DNA gyrase and with DNA supercoiling. (i) psu mutants are highly resistant to oxolinic acid, the gyrase A inhibitor, while the secondary mutants vary from being very sensitive to more resistant than the wild-type strain. (ii) Novobiocin, which decreases the level of DNA supercoiling, significantly stimulates suppression of auxotrophy in some secondary mutants.