Complete Circular Genome Sequence of Successful ST8/SCCmecIV Community-Associated Methicillin-Resistant Staphylococcus aureus (OC8) in Russia: One-Megabase Genomic Inversion, IS256’s Spread, and Evolution of Russia ST8-IV

Abstract

ST8/SCCmecIV community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been a common threat, with large USA300 epidemics in the United States. The global geographical structure of ST8/SCCmecIV has not yet been fully elucidated. We herein determined the complete circular genome sequence of ST8/SCCmecIVc strain OC8 from Siberian Russia. We found that 36.0% of the genome was inverted relative to USA300. Two IS256, oppositely oriented, at IS256-enriched hot spots were implicated with the one-megabase genomic inversion (MbIN) and vSaβ split. The behavior of IS256 was flexible: its insertion site (att) sequences on the genome and junction sequences of extrachromosomal circular DNA were all divergent, albeit with fixed sizes. A similar multi-IS256 system was detected, even in prevalent ST239 healthcare-associated MRSA in Russia, suggesting IS256’s strong transmission potential and advantage in evolution. Regarding epidemiology, all ST8/SCCmecIVc strains from European, Siberian, and Far Eastern Russia, examined had MbIN, and geographical expansion accompanied divergent spa types and resistance to fluoroquinolones, chloramphenicol, and often rifampicin. Russia ST8/SCCmecIVc has been associated with life-threatening infections such as pneumonia and sepsis in both community and hospital settings. Regarding virulence, the OC8 genome carried a series of toxin and immune evasion genes, a truncated giant surface protein gene, and IS256 insertion adjacent to a pan-regulatory gene. These results suggest that unique single ST8/spa1(t008)/SCCmecIVc CA-MRSA (clade, Russia ST8-IVc) emerged in Russia, and this was followed by large geographical expansion, with MbIN as an epidemiological marker, and fluoroquinolone resistance, multiple virulence factors, and possibly a multi-IS256 system as selective advantages.

Influence of IS 256 on Genome Variability and Formation of Small-Colony Variants in Staphylococcus aureus

“…Two examples of such deletions are present in the strains described here (Fig. S1), and interestingly, a large IS256-based genomic inversion that contains 19 copies of IS256 has been described for S. aureus OC8 (35). IS256 itself is present only in some successful MRSA lineages, most of which belong to clonal complex 8 (i.e., ST239, ST8, ST247, and ST72 [16]) (Fig.…”

Global Evolution of Pathogenic Bacteria With Extensive Use of Fluoroquinolone Agents

“…In their recent review of the USA300 MRSA ST8 clone Challagundla et al (2018a) also emphasized the relevance of the evolution of the second -gyrA Ser84Leu -mutation in the success of the lineage in the United States. Moreover, ST8 strains were reported having evolved double-serine QRDR mutations also in other geographical regions (Khokhlova et al, 2015;Glaser et al, 2016;Wan et al, 2016) that might have contributed to the dissemination of ST8 strains in France (Glaser et al, 2016) and Russia (Gostev et al, 2017). Unfortunately information on the prevalence of QRDR mutations in ST8 MRSA strains are missing from many countries.…”

Molecular-Genetic Features of Methicillin-Resistant S. Aureus, Have Got From the Persons of the Penitentiary System, Infected With Hiv

“…Проведенные в РФ исследования показали, что доминирующими в стационарах РФ являются 3 эпидемических клона MRSA: ST239/spa3(t037)/SCCmecIIIА, ST8/spa1(t00)/ SCCmecIVc, ST239/spa(t030)/SCCmecIII [20][21][22]. Есть информация о выделении ST8/spa1(t00)/SCCmecIVc во внебольничных условиях [23,24]. В США доминирующим генетическим вариантом MRSA, встречающемся среди ВИЧ-инфицированных является USA300, также относящийся к варианту ST8, характеризующийся продукцией лейкоцидина Пантон-Валентайна [25].…”