Alper M D, Ames B N
J Bacteriol. 1978 Jan;133(1):149-57. doi: 10.1128/jb.133.1.149-157.1978.
Mutants in the cyclic AMP (cAMP) control system in Salmonella 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/carbon sources. This resistance was used as the basis for an efficient positive selection of cya and crp mutants. We propose that these antibiotics and analogs enter the bacteria through transport systems normally used for transporting fuel/carbon sources and that this is accomplished because of a structural similarity between the antibiotic and the natural substrate of the particular transport system involved. We propose that these transport systems are all under positive control by cAMP and that cAMP acts as a signal molecule (alarmone) for fuel/carbon deprivation. Evidence is provided for a hierarchy within operons controlled by cAMP. The methodology is shown to be useful for analyzing both antibiotic transport systems and the cAMP super-control system.
鼠伤寒沙门氏菌中环状AMP（cAMP）控制系统的突变体（cya = 腺苷酸环化酶，crp = cAMP受体蛋白）对22种抗生素（包括磷霉素、萘啶酸和链霉素）以及29种正常细菌燃料/碳源的抑制类似物的生长抑制具有部分抗性。这种抗性被用作高效正向筛选cya和crp突变体的基础。我们提出，这些抗生素和类似物通过通常用于运输燃料/碳源的转运系统进入细菌，而这是由于抗生素与所涉及的特定转运系统的天然底物之间的结构相似性而实现的。我们提出，这些转运系统均受cAMP的正向调控，并且cAMP作为燃料/碳源剥夺的信号分子（警报素）发挥作用。为cAMP控制的操纵子内的层级关系提供了证据。该方法被证明可用于分析抗生素转运系统和cAMP超级控制系统。
