Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.

Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.

Evolution and genomic insight into methicillin-resistant Staphylococcus aureus ST9 in China.

OBJECTIVES: To reconstruct the evolutionary history and genomic epidemiology of Staphylococcus aureus ST9 in China. METHODS: Using WGS analysis, we described the phylogeny of 131 S. aureus ST9 isolates collected between 2002 and 2016 from 11 provinces in China, including six clinical samples from Taiwan. We also investigated the complex structure and distribution of the lsa(E)-carrying multiresistance gene cluster, and genotyped prophages in the genomes of the ST9 isolates. RESULTS: ST9 was subdivided into one major (n = 122) and one minor (n = 9) clade. Bayesian phylogeny predicted the divergence of ST9 isolates in pig farming in China as early as 1987, which then evolved rapidly in the following three decades. ST9 isolates shared similar multiresistance properties, which were likely acquired before the ST9 emergence in China. The accessory genome is highly conserved, and ST9 harboured similar sets of phages, but lacked certain virulence genes. CONCLUSIONS: Host exchange and regional transmission of ST9 have occurred between pigs and humans. Pig rearing and trading might have favoured gene exchanges between ST9 isolates. Resistance genes, obtained from the environment and other isolates, were stably integrated into the chromosomal DNA. The abundance of resistance genes among ST9 is likely attributed to the extensive use of antimicrobial agents in livestock. Phages are present in the genomes of ST9 and may play a role in the rapid evolution of this ST. Although human ST9 infections are rare, ST9 isolates may constitute a potential risk to public health as a repository of antimicrobial resistance genes.

Comparative analysis of genomic characteristics, fitness and virulence of MRSA ST398 and ST9 isolated from China and Germany.

Methicillin-resistant Staphylococcus aureus (MRSA) of sequence types ST398 and ST9 are dominant lineages among livestock in Europe and Asia, respectively. Although both STs were commonly found as colonizers of the skin and the mucosal membranes, MRSA ST398, rather than MRSA ST9, has been reported to cause infections in humans and animals. Herein, we comparatively analyzed the genomic characteristics, fitness and virulence of MRSA ST398 and ST9 isolated from pigs in both China (CHN) and Germany (GER) to explore the factors that lead to differences in their epidemics and pathogenicity. We observed that the CHN-MRSA ST9 and the GER-MRSA ST9 have evolved independently, whereas the CHN-MRSA ST398 and GER-MRSA ST398 had close evolutionary relationships. Resistance to antimicrobial agents commonly used in livestock, the enhanced ability of biofilm formation, and the resistance to desiccation contribute to the success of the dominant clones of CHN-MRSA ST9 and GER-MRSA ST398, and the vwbνSaα gene on the genomic island might in part contribute to their colonization fitness in pigs. All MRSA ST398 strains revealed more diverse genome structures, higher tolerance to acids and high osmotic pressure, and greater competitive fitness in co-culture experiments. Notably, we identified and characterized a novel hysAνSaß gene, which was located on the genomic island νSaß of MRSA ST398 but was absent in MRSA ST9. The enhanced pathogenicity of the MRSA ST398 strains due to hysAνSaß might in part explain why MRSA ST398 strains are more likely to cause infections.

Staphylococcus aureus isolates from Eurasian Beavers (Castor fiber) carry a novel phage-borne bicomponent leukocidin related to the Panton-Valentine leukocidin.

Staphylococcus aureus can be a harmless coloniser, but it can also cause severe infections in humans, livestock and wildlife. Regarding the latter, only few studies have been performed and knowledge on virulence factors is insufficient. The aim of the present study was to study S. aureus isolates from deceased wild beavers (Castor fiber). Seventeen isolates from eleven beavers, found in Germany and Austria, were investigated. Antimicrobial and biocide susceptibility tests were performed. Isolates were characterised using S. aureus-specific DNA microarrays, spa typing and whole-genome sequencing. From two isolates, prophages were induced by mitomycin C and studied by transmission electron microscopy. Four isolates belonged to clonal complex (CC) 8, CC12, and CC398. Twelve isolates belonged to CC1956 and one isolate was CC49. The CC49 and CC1956 isolates carried distinct lukF/S genes related to the Panton-Valentine leukocidin (PVL) from human isolates of S. aureus. These genes were located on related, but not identical, Siphovirus prophages. The beavers, from which those isolates originated, suffered from abscesses, purulent organ lesions and necrotising pneumonia, i.e., clinical manifestations resembling symptoms of severe PVL-associated disease in humans. It might thus be assumed that the "Beaver Leukocidin (BVL, lukF/S-BV)"-positive strains are beaver-specific pathogens, and further studies on their clinical role as well as on a possible transmissibility to other species, including humans, are warranted.