## 2 Local Topological Arrangement of Quorum Sensing Genes  
One of the key aspects we are interested in, is the local topology of QS genes. This concept denotes the local arrangement of QS genes with respect to each other. The local arrangements found in Proteobacteria can be classified into 16 topology groups [31]. Denoting _luxI_ genes as I, _luxR_ genes as R, we can define a number of simple topologies, such as tandem orientation ( \(\bar{R}\bar{I}\) ), convergent orientation ( \(\bar{R}\bar{I}\) ), divergent orientation ( \(\bar{R}\bar{I}\) ), _etc._ In some more complicated arrangements, there is one intervening gene between the R and I genes, and this intervening gene frequently encodes a negative regulator [31]. The _rsaL_[32; 33; 34] and the _rsaM_[31; 35; 36] genes/homologs, denoted here by L and M, respectively, are typical examples. There are further arrangements which we term complex topologies [31] in which there are several intervening genes. A further classification is based on the position of the AHL system with respect to the replication origin within the chromosome, or alternatively on which chromosome the AHL system is located. In addition to arrangement patterns, AHL systems can also be regarded as regulatory circuits that display a number of simple regulatory architectures [24; 26; 37]. The core element is the auto-inductive circuit of R and I genes that was originally used to define the concept of QS regulation [37]. However, in the absence of additional, stabilizing elements, autoinduction would raise signal levels without limit. A down-regulation loop activated at higher signal concentrations is perhaps the simplest way to limit and stabilize the signal levels. There are a variety of mechanisms that can play this stabilizing role in QS systems. For example, the master regulator TraM can form a non-functional heterodimer with the TraR gene product in _Agrobacteriumum tumefaciens_[38; 39]. A homodimer of the RasaL gene product (denoted here as L) acts as negative regulator by binding on the bi-directional _rsaL-luxl_ promoter [40]. RasaM (denoted here as M) is another small regulatory protein that might be acting in a similar way to RasaL in many _Burkholderia_ species [35]. Bacterial genomes also encode enzymes that degrade AHLs in response to the stress signal ppGpp, which can also efficiently down-regulate QS signaling [41; 42; 43; 44; 45]. Down-regulation is also thought to result from more sophisticated, RNA-mediated mechanisms [46; 47] or from the clash of transcriptional machineries on overlapping genes [48]. The crucial nature of these negative regulatory effects is shown by the fact that their deletion leads to signal overproduction and a less virulent bacterial phenotype. For the sake of completeness we also highlight that downregulation can also be automatically achieved by simple resource limitation where a reduction in number of QS cells would result in a decrease of the QS signal concentration itself [31]. Finally, yet another classification of AHL systems is possible on the basis of the chemical nature of the AHL signals they produce. It is well known that proteobacteria produce over 20 kinds of AHL signals [49; 50], although much less are produced by selected genera such as _Pseudomonas_[51]. When this article was written (data collection was finished on 18 March, 2013), the NCBI archive contained 35 complete _Burkholderia_ genomes, 57 draft genomes (30323 contigs and 266 scaffolds) and 16585 individual Genbank entries with _Burkholderia_ sequences, a small portion of which contained full or partial AHL systems. Local gene arrangements were extracted from complete, well-annotated genomes, even though we noticed that the annotation of QS genes is at times inaccurate. Draft genomes contained some annotated genes, but frequently only the contig sequences were given. Finally, individual DNA sequences in GenBank rarely contained a complete AHL system, meaning that topological data could not be abstracted.