Strain-specific daptomycin-sensitivity profiles for T4 (A) and 19F (B).

<p>Each color-coded circle (node) represents a gene depicted by its gene number (note that all numbering is according to strain T4; for strain specific numbers see the correspondence table in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005869#ppat.1005869.s013" target="_blank">S8 Table</a>), that is connected by a line (edge) to daptomycin in the center of the network. The edge indicates that the gene’s fitness significantly changes in the presence of daptomycin; a black edge indicates fitness is significantly lower, while a green edge indicates fitness increases. A node with a dotted border indicates that its phenotype is not conserved in the other strain, while a solid black border indicates its phenotype is conserved, unless there is a dash underneath the gene-number which means it was impossible to determine whether the phenotype was conserved in the other strain due to too little insertions. If a gene-number starts with SP or SPT, the gene is strain-specific in T4 or 19F respectively. Some sets of genes are highlighted in the networks by indicating their functional role (<i>e</i>.<i>g</i>. peptidoglycan, ClpP) or by arrows that represent relationships (e.g. SP1732/SP1733 have a regulatory effect on peptidoglycan). Genes with unknown function are depicted in white, and if they have a close neighbor with an annotated function in the network they are placed next to that neighbor, possibly suggesting a shared role. Next to each network the importance of each functional category in the network is ranked by the number of genes present in the network. Finally, as described in more detail in the main text, and to illustrate that the antibiotic interacts with the bacterium on different organizational levels, each functional category belongs to one of four hierarchical layers which combines the physical location of the gene-product with its molecular function. The first layer consists of capsule and peptidoglycan genes and is both the first layer of protection from, and interaction with, the outside world. The second layer is important for membrane integrity and transport across the membrane represented by membrane, lipoprotein and transporter genes. The third layer controls and orchestrates fundamental processes including cell division, transcription and translation and regulation, while the fourth combines all metabolism genes. The importance of each layer is highlighted by the thickness of the layer, which is determined by the number of genes in that layer, while within each layer the importance of each category is represented as a percentage.