New resistance mutations linked to decreased susceptibility to solithromycin in Streptococcus pneumoniae revealed by chemogenomic screens

We obtained a series of Streptococcus pneumoniae mutants resistant to solithromycin that were characterized by next generation sequencing. We found mutations in various ribosomal proteins (L3, L4, L22, L32, S4) and in the 23S rRNA. We also found mutations in subunits of the phosphate transporter, in the Dead box helicase CshB and in the ermBL leader peptide. These include novel phenotypic mutations in the intergenic regions of the mef(E)/mel efflux pumps and in the vicinity of the ribosome binding site of ermB. Our screens highlighted that macrolide resistant S. pneumoniae can easily acquire resistance to solithromycin and revealed many new phenotypic mutations.