[Frontiers in Bioscience 9, 2909-2926, September 1, 2004] 2909 SENSING AND ADAPTING TO ENVIRONMENTAL STRESS: THE ARCHAEAL TACTIC Emilia Pedone 1 , Simonetta Bartolucci 2 and Gabriella Fiorentino 2 1 Istituto di Biostrutture e Bioimmagini , C.N.R., Via Mezzocannone 6, 80134, Napoli, Italy, 2 Dipartimento di Chimica Biologica, Università degli Studi di Napoli Federico II, Via Mezzocannone 16-80134, Napoli, Italy TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Oxidative stress 3.1. Thioredoxin/glutaredoxin 3.2. Peroxiredoxins 3.3. Hydroperoxidases 3.4. NADH oxidase 3.5. Oxygen detoxification without superoxide dismutase 3.6. Superoxide dismutase 4. Chemical stress 4.1. Metal detoxification 4.1.1. Metal reductases 4.1.2. Efflux pumps, membrane-bound transporters 4.1.3. Transcriptional regulatory proteins 4.2. Drug detoxification 4.2.1. The ATP binding cassette superfamily 4.2.2. Secondary multidrug transporters 4.2.3. Regulation of multidrug transporter genes 4.2.4. Metabolic detoxification 5. Concluding remarks 6. Acknowledgements 7. References 1. ABSTRACT Archaea occupy a considerable diversity of niches encompassing extreme environments with extreme of pH, salinity and temperature that cannot be tolerated by other forms of life. Survival and colonisation requires the capacity to sense, and adapt to environmental change. In this review we consider the issues of adaptation to environmental stresses, in particular the mechanisms that might be employed by different Archaea to respond to the specific challenges of their particular niche. We lay emphasis on the strategies adopted to respond to oxidative and chemical stress. In particular, this paper reviews major key points in the generation of reactive oxygen species in Archaea, defense mechanisms and genetic responses to oxidative stress. Finally, we discuss complex biological response mechanisms to chemical damage with particular attention to detoxification from metals and drugs. 2. INTRODUCTION The third domain of life, Archaea, encompasses organisms capable of growing under extreme conditions of pH, salinity, temperature (1). During evolution, each organism thriving in hard conditions has acquired genotypes that fit for their adaptation and survival in that particular niche. Many external agents of biological, physical or chemical nature, like temperature, ion concentration, oxygen availability, osmolarity, metal and pollutant concentrations, can determine a further stress for the cell and hence it appears critical to sense and to adapt to rapid and subtle changes in the environment. The molecular mechanisms responsible for response to environmental stress have been only partially elucidated in some Archaea by identifying proteins/enzymes or pathways directly involved in counteracting the effect of the stress agents (2) (figure 1). By homology to better established bacterial counterparts, it has emerged that the strategies adopted correlate with the organism’s lifestyle. For example, anaerobic euryarchaea, like Pyrococcus furiosus or Archaeoglobus fulgidus, have developed alternative or redundant pathways with unique and interesting features both at molecular and evolutionary levels to protect from oxidative damage (3, 4). The relevance of such peculiar means is demonstrated by the fact that these systems are so finely regulated. The recent intense development in genome sequencing and the completion of several sequencing projects of Archaea now available in specific data-bases (5), allowed in silico analyses focused in identifying complex regulated biochemical pathways. This new tool, alongside with comparative genomics and functional genomic studies, can help in unravelling how these microbes survive, adapt to their environment and lifestyle,