Balancing selection near the active site of multidrug efflux pump of multiple bacterial genera
To visualize the location of the AcrB CORF inferred to be under balancing selection in Bacteroides dorei , this sequence was searched against the Protein Data Bank. This analysis yielded a top hit of a multidrug efflux pump from Escherichia coli. Alignment of the B. dorei AcrB CORF against the E. coli reference enabled visualization of the putative location of the B. doreiAcrB CORF’s peptide in the multidrug efflux pump. The crystal structure of this E. coli protein with the homologous region from B. dorei indicated is presented in Figure 2B. Theses analyses revealed that the peptide lays within a binding site of the protein complex. Ligands that interact with AcrB in E. coli include several notable antibiotics such as Erythromycin A, a macrolide, and Minocycline, a tetracycline. The binding site of Erythromycin A, which includes residues in AcrB, is shown in Figure 2C. To further investigate the potential functional significance of the B. dorei AcrB CORF, we conducted analyses of disorder and hydrophobicity, both of which are expected to differ near active sites of protein complexes from the background levels. These analyses indicated that this AcrB CORF codes for a peptide with relatively low levels of disorder and high hydrophobicity (Figure S1).