Effects of metabolic flux on stress response pathways in Lactococcus lactis

Studies of cellular responses to stress conditions such as heat, oxygen or starvation have revealed the existence of numerous specific or interactive response pathways. We previously observed in Lactococcus lactis that inacti vation of the recA gene renders the lactococcal strain sensitive not only t o DNA-damaging agents but also to oxygen and heat. To further examine the s tress response pathways in L. lactis, we isolated (t) under bar hermo (r) u nder bar esistant insertional (m) under bar utants (Trm) of the recA strain . Eighteen independent trm mutations were identified and characterized. We found that mutations map in only seven genes, implicated in purine metaboli sm (deoB, guaA and tktA), phosphate uptake (pstB and pstS), mRNA stability (pnpA) and in one uncharacterized gene (trmA). All the trm mutations, with the exception of trmA, confer multiple stress resistance to the cell. Some of the mutations confer improved heat stress resistance not only in the rec A but also in the wild-type context. Our results reveal that cellular metab olic pathways are intimately related to stress response and that the flux o f particular metabolites, notably guanine and phosphate, may be implicated in stress response in lactococci.