Various Mobile Genetic Elements Involved in the Dissemination of the Phenicol-Oxazolidinone Resistance Gene optrA in the Zoonotic Pathogen Streptococcus suis: a Nonignorable Risk to Public Health

Abstract

ABSTRACT The rapid increase of phenicol-oxazolidinone (PhO) resistance in Streptococcus suis due to transferable resistance gene optrA is a matter of concern. However, genetic mechanisms for the dissemination of the optrA gene remain to be discovered. Here, we selected 33 optrA-positive S. suis isolates for whole-genome sequencing and analysis. The IS1216E element was present in 85% of the optrA-carrying contigs despite genetic variation observed in the flanking region. IS1216E-optrA-carrying segments could be inserted into larger mobile genetic elements (MGEs), including integrative and conjugative elements, plasmids, prophages, and antibiotic resistance-associated genomic islands. IS1216E-mediated circularization occurred to form the IS1216E-optrA-carrying translocatable units, suggesting a crucial role of IS1216E in optrA spreading. Three optrA-carrying MGEs (ICESsuAKJ47_SSU1797, plasmid pSH0918, and prophage ΦSsuFJSM5_rum) were successfully transferred via conjugation at different transfer frequencies. Interestingly, two types of transconjugants were observed due to the multilocus integration of ICESsuAKJ47 into an alternative SSU1943 attachment site along with the primary SSU1797 attachment site (type 1) or into the single SSU1797 attachment site (type 2). In addition, conjugative transfer of an optrA-carrying plasmid and prophage in streptococci was validated for the first time. Considering the abundance of MGEs in S. suis and the mobility of IS1216E-optrA-carrying translocatable units, attention should be paid to the potential risks to public health from the emergence and spread of PhO-resistant S. suis. IMPORTANCE Antimicrobial resistance to phenicols and oxazolidinones by the dissemination of the optrA gene leads to treatment failure in both veterinary and human medicine. However, information about the profile of these MGEs (mobilome) that carry optrA and their transferability in streptococci was limited, especially for the zoonotic pathogen S. suis. This study showed that the optrA-carrying mobilome in S. suis includes integrative and conjugative elements (ICEs), plasmids, prophages, and antibiotic resistance-associated genomic islands. IS1216E-mediated formation of optrA-carrying translocatable units played important roles in optrA spreading between types of MGEs, and conjugative transfer of various optrA-carrying MGEs (ICEs, plasmids, and prophages) further facilitated the transfer of optrA across strains, highlighting a nonignorable risk to public health of optrA dissemination to other streptococci and even to bacteria of other genera.

Keywords

• Streptococcus suis
• PhO resistance
• optrA
• horizontal gene transfer
• IS1216E
• antimicrobial resistance