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).