Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants

Abstract

Mutants in the cyclic(c)AMP control system in S. typhimurium (cya = adenyl cyclase, crp = cAMP receptor protein) were partially resistant to growth inhibition by 22 antibiotics (including fosfomycin, nalidixic acid and streptomycin) and 29 inhibitory analogs of normal bacterial fuel/C sources. This resistance was used as the basis of an efficient positive selection of cya and crp mutants. These antibiotics and analogs enter the bacteria through transport systems normally used for transporting fuel/C sources and this is accomplished because of a structural similarity between the antibiotic and the natural substrate of the particular transport system involved. These transport systems are all under positive control by cAMP and cAMP acts as a signal molecule (alarmone) for fuel/C deprivation. Evidence is provided for a hierarchy within operons controlled by cAMP. The methodology is useful for analyzing both antibiotic transport systems and the cAMP super-control system.