Genome-Wide Analysis of Gene Expression in Stationary Phase and Genetic Characterization of Stationary-Phase-Dependent Halocin Gene Expression in the Haloarchaeon Haloferax mediterranei

Abstract

Haloarchaea are adapted to survive under extreme saline conditions by accumulating osmolytes and salts to counteract the high osmotic pressure in their habitats. As a consequence, their proteins have evolved to remain active, or even most active, at very high ionic strength. Halocins are proteinaceous antimicrobial substances that are ribosomally-synthesized by haloarchaea and they provide the producers an advantage in the competition for nutrients and ecological niches. These antimicrobials are stable at high temperature, elevated salt concentrations, and alkaline pH conditions. These properties have endowed them with great potential in diverse biotechnological applications, which involve extreme processing conditions (such as high salt concentrations, high pressure, or high temperatures). They kill target cells by inhibition of Na+/H+ antiporter in the membrane or modification/disruption of the cell membrane leading to cell lysis. In general, the taxonomy of haloarchaea and their typical phenotypic and genotypic characteristics are well studied; however, information regarding their halocins, especially aspects related to genetics, biosynthetic pathways, mechanism of action, and structure-function relationship is very limited. A few studies have demonstrated the potential applications of halocins in the preservation of salted food products and brine-cured hides in leather industries, protecting the myocardium from ischemia and reperfusion injury, as well as from life-threatening diseases such as cardiac arrest and cancers. In recent years, genome mining has been an essential tool to decipher the genetic basis of halocin biosynthesis. Nevertheless, this is likely the tip of the iceberg as genome analyses have revealed many putative halocins in databases waiting for further investigation. Identification and characterization of this source of halocins may lead to antimicrobials for future therapeutics and/or food preservation. Hence, the present review analyzes different aspects of halocins such as biosynthesis, mechanism of action against target cells, and potential biotechnological applications.