Lateral transfer and GC content of bacterial resistance genes

Lateral genetic transfer (LGT) is one of the ways in which microorganisms such as bacteria could move and rearrange genetic materials from and into their genomes (Ragan and Beiko, 2009). The dissemination of antibiotic resistance genes between two microorganisms or between a microorganism and the environment could occur, for example, by conjugation, transduction, and transformation (Fondi and Fani, 2010; Stokes and Gillings, 2011). Therefore, having a resistance gene or genes on a mobile element like plasmids and genomic islands, transposons, integrons, or integrative conjugative elements will facilitate their overall distribution, which will affect among other organisms, humans andmore specifically their health and survival (Stokes and Gillings, 2011). This fact, made the selection for antibiotic resistance a crucial step in microorganism’s selective evolution (Waksman and Woodruff, 1940). However, even though this selection is enhanced and accelerated by the use of antibiotics (Hegreness et al., 2008), the acquisition of a new genetic material is balanced by mechanisms that restrict DNA uptake (Navarre et al., 2006; Palmer and Gilmore, 2010). One of these mechanisms is the clustered regularly interspaced short palindromic repeat (CRISPR) (van der Oost et al., 2009), which was found to be negatively related to the number of acquired resistant genes in a Enterococcus faecalis (Palmer and Gilmore, 2010). Moreover, a closer look at the multidrug resistance genomic regions in bacteria shows that they could be collected from different mobile genetic elements to form what is known as pathogenicity islands (Dobrindt et al., 2004; Fournier et al., 2006; Adams et al., 2008; Hall, 2010). And contrary to higher organisms, bacterial genetic material exchange occurs between close or distant relatives spanning the three domains of life (Garcia-Vallvé et al., 2000; Mallet, 2008). Based on the previous findings, characterizing the antibiotic resistome is becoming highly important in order to detect yet unknown resistance mechanisms and to develop new antibiotics that help in the fight against potential resistant organisms (D’Costa et al., 2006). The guanine-cytosine (GC) composition of bacterial genomes is one of the genomic taxonomic markers and a genomic signature that is considered a tool for comparison between chromosomes and plasmids (Nishida, 2012), and for distinguishing genes according to their method of transfer, i.e., horizontally or vertically (Garcia-Vallvé et al., 2000). Therefore, could such a tool provide distinctive information about resistant genes and pathogenicity islands in the sourcesink model of LGTs (Miura, 1962; Pulliam, 1988; Garcia-Vallvé et al., 2000; Bohlin, 2011)? In other words, could the GC content difference between the resistant gene/pathogenicity island and its genomic context play a role in the structure and function of the host bacterium, regardless if it was acquired horizontally or vertically? Finally, could the GC content of resistant genes be incorporated in the antibiotic resistome study (D’Costa et al., 2006)? The fact that the complete genome sequences of many bacterial and archaeal species are still unavailable makes the answers to these questions incomplete and awaiting for more sequences to be finalized. However, several studies tried to tackle these issues. For instance, Garcia-Vallvé et al. (2000) developed a statistical method to identify potential genes that were recently horizontally transferred and classified them according to their general functions. In another study Hildebrand et al. (2010), concluded that contrary to the GC to AT mutation pattern detected in the tested bacterial species, the genomic GC content is not correlated to the this mutation bias and species were able to maintain their higher than expected GC%. Similar results were obtained by other groups (Hershberg and Petrov, 2010; Nishida, 2012), who were able to highlight the tendency to preserve a higher genomic GC content in spite of the AT mutation bias. To explain their data, the authors (Hildebrand et al., 2010) suggested a potential selective pressure that controls the GC content in certain bacterial species with high GC content. In their recent article Raghavan et al. (2012), explored this concept further. They were able to show a significant positive correlation between the expression of a transferred protein-coding gene with a high GC content and bacterial fitness. Therefore, according to the authors, this indicates that a significantly better growth rate compensates for the AT mutation bias and a better fitness could be the driving factor for maintaining a higher GC content in at least the tested bacterial strains. Based on the discussed studies, two groups of challenges could be highlighted. The first group is related to the conducted studies and the methodologies used. The second, is related to the mutual evolutionary effects between the GC content of resistance genes and pathogenicity islands on one side and the genomic GC content on the other. Regarding the first group, a recently published study (Becq et al., 2010) shows that detecting LGT using one method could be arduous and a combination of two methods is recommended to improve the sensitivity and the specificity of the applied method. In addition, most of the studies tries to identify recently transferred genetic material without following the evolution of the transferred