Identification and pathogenicity of an XDR Streptococcus suis isolate that harbours the phenicol-oxazolidinone resistance genes optrA and cfr, and the bacitracin resistance locus bcrABDR

• An extensively-drug-resistant Streptococcus suis isolate, SFJ44, was isolated from the nasal swab of an asymptomatic pig in Jiangsu, China in 2017. • This isolate harboured the phenicol-oxazolidinone resistance genes optrA and cfr , and the bacitracin resistance locus bcrABDR. • Circular intermediates of bcrABDR -IS Enfa1 were observed. • This isolate had a virulence level comparable to S. suis serotype 2 hypervirulent strain SC070731. One hundred and seven Streptococcus suis isolates were collected from healthy pigs or asymptomatic carriers in Jiangsu, China in 2016–2017. Thirty-eight percent of the isolates were linezolid-resistant and all carried the optrA gene. Among them, one isolate, SFJ44, was resistant to all 20 of the antibiotics tested, except for ceftiofur, and thus exhibited an extensively-drug-resistant phenotype. This isolate carried the optrA gene and the bacitracin resistance locus bcrABDR on an antibiotic-resistance-associated genomic island (ARGI1), and harboured the resistance genes cfr, aadE, sat4, spw -like, aphA3, mef (A) , msr (D) , erm (A)-like, erm (B), tetAB (P)', tet (M) and catQ on ARGI2∼4. The IS 1216E - bcrABDR -IS Enfa1 segment showed >99.9% sequence identity to corresponding sequences from other species. The cfr gene was located on ARGI4, and two IS 6 family insertion sequences, IS 1216E and IS Teha2 , were found upstream and downstream of cfr -ΔIS Enfa5 , respectively. A circular intermediate of bcrABDR -IS Enfa1 was detected, suggesting the role of IS Enfa1 in dissemination of bcrABDR . Other antibiotic resistance genes might be acquired from different Gram-positive pathogens. Infection of zebrafish showed that SFJ44 exhibited a virulence level comparable to serotype 2 hypervirulent strain SC070731, highlighting the need for surveillance of the pathogenicity of multi-drug-resistant S. suis isolates. This is the first report of the co-existence of optrA and cfr , and of the bcrABDR locus in streptococci. As it has been suggested that S. suis may act as an antibiotic resistance reservoir contributing to the spread of resistance genes to major streptococcal pathogens, the potential dissemination of these resistance genes among Gram-positive bacteria is of concern and routine surveillance should be strengthened.