It is now recognized that membranes are not simple physical barriers but represent a complex and dynamic environment that affects membrane protein structures and their functions. Recent data emphasize the role of membranes in sensing temperature changes, and it has been shown that the physical state of the plasma membrane influences the expression of a variety of genes such as heat shock genes. It has been widely shown that minor alterations in lipid membranes are critically involved in the conversion of signals from the environment to the transcriptional activation of heat shock genes. Previously, we have proposed that the composition, molecular arrangement, and physical state of lipid membranes and their organization have crucial roles in cellular responses during stress caused by physical and chemical factors as well as in pathological states. Here, we show that transformation of Salmonella enterica serovar Typhimurium LT2 (Salmonella Typhimurium) with a heterologous ⌬ 12 -desaturase (or with its trans-membrane regions) causes major changes in the pathogen's membrane dynamic. In addition, this pathogen is strongly impaired in the synthesis of major stress proteins (heat shock proteins) under heat shock. These data support the hypothesis that the perception of temperature in Salmonella is strictly controlled by membrane order and by a specific membrane lipid/protein ratio that ultimately causes transcriptional activation of heat shock genes. These results represent a previously unrecognized mode of sensing temperature variation used by this pathogen at the onset of infection.The heat shock response, one of the most studied cellular homeostatic mechanisms, is involved in the maintenance of cell functionality during stress (25, 60). The heat shock response is also elicited by pathogens at the onset of infection as a result of exposure to environmental stresses such as a heat shock or during macrophage infection (25,55). In addition, the heat shock response is severely altered as a result of several chronic diseases, cancer, apoptosis, and the aging process (3, 27, 45). The resulting protection from different types of stresses is due to the transcriptional activation of heat shock genes (29, 54). Further, moderate heat (or stress) treatment induces transient acquisition of thermotolerance, even in the absence of denatured proteins (40, 51), due to the accumulation of heat shock proteins (HSPs) (35). These proteins are not only essential under a variety of stress conditions, such as heat, drought, salinity, osmotic shock, membrane shearing, ischemia, etc. (11,23,55,67), but are also crucial under physiological conditions for protein folding, translocation, mRNA splicing, nucleic acid and protein syntheses, mitochondrial electron transport, and photosynthesis, for example (4,24,25,39). Members of the group of small HSPs (sHSPs) have also been shown to antagonize heat-induced membrane hyperfluidization and to stabilize the bilayer state under stress conditions (40,54,59).According to the conventional model, during s...