Synergy between efflux pump CmeABC and modifications in ribosomal proteins L4 and L22 in conferring macrolide resistance in Campylobacter jejuni and Campylobacter coli

Abstract

Macrolide-resistant mutants of Campylobacter jejuni and Campylobacter coli were selected in vitro using erythromycin and tylosin. These mutants exhibited modifications in the ribosomal proteins L4 (G74D) and L22 (insertions at position 86 or 98). A synergy between the CmeABC efflux pump and these modifications in conferring macrolide resistance was observed.

FIG. 1.

Comparison of the L4 (A) and L22 (B) protein sequences of Campylobacter and other bacterial species: D. radiodurans, Deinococcus radiodurans R1 (NP_294035 and NP_294039); E. coli, Escherichia coli K-12 (AAC76344 and AAC76340); H. influenzae, Haemophilus influenzae Rd KW20 (NP_438937 and NP_438941); M. pneumoniae, Mycoplasma pneumoniae M129 (NP_109854 and NP_109858); S. aureus, Staphylococcus aureus MRSA252 (CAG41315 and CAG41311); S. pneumoniae, Streptococcus pneumoniae R6 (AAK98993 and NP_357788); S. pyogenes, Streptococcus pyogenes M1 group A streptococcus (AAK33183 and AAK33187); Cj, Campylobacter jejuni 11168, NCTC 11168 (CAB73692 and CAB73688), RM1221 (YP_179844 and YP_179840), CF93-6 (ZP_01067485 and EAQ57344), 81-176 (ZP_01087492), 260-94 (ZP-01070430), 84-25 (EAQ95418), HB93-13 (ZP_01070671), 87072 (AAY88727), 88375 (AAY88729), CIT-423 (AAY88725), CIT-424 (AAY88726), CIT-428 (AAZ14851); Cc, Campylobacter coli RM2228 (ZP-00370771), 98178 (AAY88728). Accession numbers in parentheses are given respectively for the L4 and L22 protein sequences of each bacterium (or for the L22 protein alone if no sequence of the L4 protein is available). Accession numbers of newly deposited sequences appear in the text. The arrows indicate the modifications occurring in the in vitro-selected mutants. The most conserved residues are underlined. Nucleotide and amino acid alignments were generated using the Vector NTI software Suite 9 (Informax, Frederick, MD). Strains with identical protein sequences appear on the same line.