title: Multi-stress resistance in Lactococcus lactis is actually escape from purine-induced stress sensitivity.
abstract: Multi-stress resistance is a widely documented and fascinating phenotype of lactococci where single mutations, preferentially in genes involved in nucleotide metabolism and phosphate uptake, result in elevated tolerance to multiple stresses simultaneously. In this report, we have analysed the metabolic basis behind this multi-stress-resistance phenotype in Lactococcus lactis subsp. cremoris MG1363 using acid stress as a model of multi-stress resistance. Surprisingly, we found that L. lactis MG1363 is fully resistant to pH 3.0 in the chemically defined SA medium, contrary to its sensitivity in the rich and complex M17 medium. When salvage of purines and subsequent conversion to GTP was permitted in various genetic backgrounds of L. lactis MG1363, the cells became sensitive to acid stress, indicating that an excess of guanine nucleotides induces stress sensitivity. The addition of phosphate to the acid-stress medium increased the stress sensitivity of L. lactis MG1363. It is also shown that high intracellular guanine nucleotide pools confer increased sensitivity to high temperatures, thus showing that it is indeed a multi-stress phenotype. Our analysis suggests that an increased level of guanine nucleotides is formed as a result of an improved conversion of guanosine in the salvage pathway. Based upon our findings, we suggest that L. lactis MG1363 is naturally multi-stress resistant in habitats devoid of any purine source. However, any exogenous purine that results in increased guanine nucleotide pools renders the bacterium sensitive to environmental stresses.
authors.affiliation: Department of Food Science, Food Microbiology, Faculty of Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Mia
authors.initials: M
authors.lastname: Ryssel
authors.affiliation: Metabolic Signaling and Regulation Group, DTU Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Anne-Mette Meisner
authors.initials: AM
authors.lastname: Hviid
authors.affiliation: Metabolic Signaling and Regulation Group, DTU Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Dawish
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Haaber
authors.affiliation: Metabolic Signaling and Regulation Group, DTU Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: Hammer
authors.affiliation: Metabolic Signaling and Regulation Group, DTU Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Martinussen
authors.affiliation: Metabolic Signaling and Regulation Group, DTU Systems Biology, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Mogens
authors.initials: M
authors.lastname: Kilstrup
mesh_terms: D000143:Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D013294:Lactococcus lactis / Q000235:genetics / Q000502:physiology*; D011687:Purines / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D011687:Purines; C030985:purine