**6. Bacterial FAS1 Proteins**

The most thoroughly studied eubacterial FAS1 proteins are the homologues Mpb70 and Mpb83 from *Mycobacterium* (reviewed in [171]). In various genomes of obligate pathogenic, opportunistic and non-pathogenic mycobacteria [172], both non-pathogenic and pathogenic species contained *Mpb70/Mpb83* homologues, while the genomes of opportunistic mycobacteria did not. This suggests a relation of *Mpb70/Mpb83* to mycobacterial lifestyle and pathogenesis. While Mpb83/Mpb70 was hypothesized to undergo "homophilic" interactions with mammalian Pn thereby interfering with cell adhesion in bones [171] this idea is not compatible with the secreted nature of Pn and is derived from cell aggregation data [8,173], which could have alternative explanations. Moreover, no intermolecular interactions between Fas1 domains have been reported. However, both host cell to ECM adhesion and host cell to mycobacterium adhesion might be modulated by binding of Mpb70/Mpb83 to molecules presented at the host cell surface. Indeed, Mpb83 was demonstrated to bind to Toll-like receptors 1 and -2 (HsTlr1 and -2), two LRR-RLKs present on human monocytes [41]. The binding of recombinant Mpb83 to HsTlr2 triggered mitogen activated protein kinase (MAPK) signaling and as a consequence induced the production of matrix metalloprotease-9 (MMP-9) and cytokines [174]. The direct interaction between Tlr2 and Mpb83, as shown by surface plasmon resonance [41], is an intriguing finding, given the presence of more than 200 LRR-RLKs in plant genomes [175]. A role of bacterial FAS1 proteins in the interaction between bacteria and their eukaryotic hosts is also observed in symbiotic communities. In the first example, the FAS1 protein SmNex18 (locus SMa1077) of the nitrogen-fixing legume symbiont *Sinorhizobium meliloti* was shown to be expressed specifically during nodulation, the initial stage of symbiosis between bacterium and plant [176,177]. Secondly, a FAS1 protein was found in *Nostonoc* cyanobacteria that form symbiotic bacterial–fungal communities called lichen. *Nostonoc punctiforme* isolates living in lichen highly expressed an unnamed FAS1 protein (locus ACC81089) that was only a minor compound in a closely related free living strain [178]. Moreover, FAS1 proteins featured prominently in the metaproteome of phyllospheric (i.e., plant leaf dwelling) bacteria [179] but were absent from rhizospheric (root-dwelling) bacteria [180]. Likewise, while present in many different genera of archaea, the FAS1 domain is not necessarily ubiquitous within the same genus. To give an example, among the 13 completely sequenced *Methanobacterium* isolates, only *M. paludis* isolated from peatland contained FAS1 domain protein sequences [181]. On the one hand, such

circumstantial observations support the hypothesis that FAS1 proteins are important for the interaction between prokaryotic colonizers and eukaryotic hosts; on the other hand, they also show that FAS1 proteins are not essential.
