Transcriptional Regulation inYersinia: An UpdateYersinia: An Update

Abstract

In response to the ever-present need to adapt to environmental stress, bacteria have evolved complex (and often overlapping) regulatory networks that respond to various changes in growth conditions, including entry into the host. The expression of most bacterial virulence factors is regulated; thus the question of how bacteria orchestrate this process has become a recurrent research theme for every bacterial pathogen, and the three pathogenic Yersinia are no exception. The earliest studies of regulation in these species were prompted by the characterization of plasmid-encoded virulence determinants, and those conducted since have continued to focus on the principal aspects of virulence in these pathogens. Most Yersinia virulence factors are thermally regulated, and are active at either 28°C (the optimal growth temperature) or 37°C (the host temperature). However, regulation by this omnipresent thermal stimulus occurs through a wide variety of mechanisms, which generally act in conjunction with (or are modulated by) additional controls for other environmental cues such as pH, ion concentration, nutrient availability, osmolarity, oxygen tension and DNA damage. Yersinia's recent entry into the genome sequencing era has given scientists the opportunity to study these regulators on a genome-wide basis. This has prompted the first attempts to establish links between the presence or absence of regulatory elements and the three pathogenic species' respective lifestyles and degrees of virulence. IntroductionCompared to cells of multicellular organisms, microorganisms face a significant additional challenge: they encounter a wide array of sudden, intense and sometimes even life-threatening environmental changes, and must therefore rapidly modify their structure and metabolism accordingly. Although other mechanisms exist, these changes in bacterial physiology mainly occur by regulating the production of the appropriate structural proteins and enzymes. Adaptation of gene expression in response to such situations appears to be essential for bacterial survival, and thus the regulators involved in these processes should be treated as being as important as the effectors themselves. In bacterial pathogens like those of the Yersinia genus, most outside-to-inside stressinduced responses lead to changes in the expression of virulence factors. In fact, most of the known Yersinia virulence genes are regulated, and elements controlling their expression are thus also virulence factors.All regulatory systems have a common purpose: to create an interface between the perception of one or several stimuli and to activate or repress expression of their cognate effectors. As we will see by reviewing what is known about Yersinia, the means used to regulate the production of a given bacterial factor range from very simple mechanisms (where the DNA-binding properties of the transcriptional regulator are directly altered by the stimulus) to extremely complex systems which sometimes require lengthy signal transduction cascades and/or simul...