These examples demonstrate that although some metal sensor systems can detect more than one metal, they are generally remarkably metal-specific, highlighting also the need for a large amount of sensor systems to maintain cellular metal homeostasis. The genus Pseudomonas includes a great variety of widely distributed buy EPZ015666 species that are known for their metabolic versatility and remarkable environmental adaptability [23]. Many pseudomonads are intrinsically highly resistant to different toxic compounds such as antibiotics, aromatics, detergents and heavy metals SB525334 nmr [24], which can be explained not only by their low outer membrane permeability and the presence of multiple efflux systems, but also by the large number of

two-component signaling systems that are potentially able to shape the bacterial response to external stressors [25]. Interestingly, only a few metal resistance-regulating two-component systems have been characterized in pseudomonads so far. CzcRS has been described as a zinc-responsive system conferring resistance to

zinc, cadmium and cobalt, but also to the antibiotic imipenem [26]. CopRS is a copper-activated signal system, which is required for copper resistance in P. aeruginosa [27], but also contributes to zinc resistance by activating the czcRS operon [28]. Contrarily, the CopRS ortholog of P. fluorescens seems to behave as a copper deficiency sensor that activates copper uptake when necessary [29]. This illustrates that even highly related sensor systems may sense and respond to different stimuli. Another example of that kind is PmrAB, which responds to external iron and alleviates iron toxicity in Salmonella see more enterica [16, 18], but its ortholog in P. aeruginosa is not involved in iron resistance [30]. One of the well-conserved two-component systems in pseudomonads is the ColRS signaling pathway [31]. Its orthologs are also present in other environmental bacteria but seem to be absent from enteric bacteria. The ColRS system was first described as a root colonization factor of P. fluorescens [32]. Recent reports indicate that ColRS signaling is also important for the virulence of P. aeruginosa [33] and plant pathogenic Xanthomonas species [34, 35]. ColRS deficiency

results in pleiotropic effects in P. putida, Idoxuridine including lowered phenol tolerance [36, 37] and subpopulation lysis when bacteria grow under glucose limitation [38, 39]. The phenotypic effects of ColRS deficiency as well as the identified target genes of the regulator ColR suggest that the ColRS system is involved in the regulation of membrane functionality [34, 36, 38, 40, 41]. However, so far the molecular basis of the membrane stress of the colR mutant as well as the signal sensed by ColS has remained unclear. Interestingly, recent reports suggest that the ColRS system may be involved in metal homeostasis, as it contributes to the copper tolerance of X. citri [34], cadmium tolerance of X. campestris [42] and multi-metal resistance of P. putida CD2 [43].