Analyses of diverse bacterial genomes suggest that partner-switching orthologues may exist in a wide range of eubacteria (Mittenhuber, 2002; Mattoo et al., 2004). Despite its predicted widespread distribution, partner switching has remained relatively uncharacterizedwithin Gram-negative bacteria. Indeed, partner-switching systems have been characterized in only two Gram-negative bacteria, Bordetella bronchiseptica and Chlamydia trachomatis (Kozak et al., 2005; Hua et al., 2006). Furthermore, only in the case of B. bronchiseptica has a partner-switching module been experimentally demonstrated to regulate a physiological response. This respiratory pathogen utilizes a partner-switching module to control production of a type III secretion system (T3SS) (Mattoo et al., 2004). The T3SS consists of a needle-like secretory apparatus that directly transports virulence proteins into the cytoplasm of host cells. In B. bronchiseptica, the T3SS contributes to persistent colonization of the host trachea and the avoidance of the host immune response (Yuk et al., 2000; Mattoo et al., 2001). The production of the T3SS requires transcription of a gene cluster, the bsc locus, which encodes multiple components of the secretory system (Mattoo et al., 2001). Regulation of the T3SS depends upon a set of genes adjacent to the bsc cluster, the btr locus, which encode orthologues of the B. subtilis RsbU/V/W partner-switching proteins, BtrU/BrtV/BtrW.In vitro and in vivo analyses of the B. bronchiseptica proteins demonstrated that they constitute a regulatory network similar to their B. subtilis counterparts (Kozak et al., 2005). However, this partner-switching system appears to deviate from that of the B. subtilis RsbU/V/W paradigm. First, disruption of any component of the BtrU/V/W partner-switching module results in the loss of type III secretion (Mattoo et al., 2004), a result that is inconsistent with the B. subtilis model (Fig. 4A). Second, positive regulation of the T3SS requires both the formation of the BtrV/BtrW complex and its dissociation, via phosphorylation of BtrV by BtrW (Kozak et al., 2005). Finally, although the BtrU/V/W module regulates type III secretion, it does not appear to control transcription of the bsc locus (Kozak et al., 2005). Instead, Kozak and colleagues (2005) suggest that these partner-switching proteins may regulate the T3SS at the posttranscriptional level possibly by interacting with yet unknown regulatory proteins or playing a structural role in the secretory pathway. Thus, although there is conservation of the partner-switching components, the regulatory mechanism appears to vary from that of the Gram-positive paradigm.
Genome analysis of the obligate intracellular pathogen C. trachomatis identified several components of a putative partner-switching module (Hua et al., 2006). In vitro analysis of the candidate genes demonstrated that these proteins could interact. As with B. bronchiseptica, it appears that the C. trachomatis partner-switching system may vary from the B. subtilis paradigm, as in vitro binding assays failed to demonstrate an interaction with any of the three sigma factors encoded in the C. trachomatis genome (Hua et al., 2006). However, the lack of genetic tools and difficulty in culturing C. trachomatis have delayed analysis of this potential partner-switching module in vivo.
Together, these studies suggest that the partner-switching mechanism, previously observed only among the Gram-positives, also contributes to regulatory control in Gram-negative bacteria. It remains unknown how these Gram-negative partner-switching proteins regulate downstream targets. Furthermore, it remains unclear how widespread this regulatory mechanism is among Gram-negative bacteria.