Healthcare- and Community-Associated Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution

<div><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a common multidrug-resistant (MDR) pathogen. We herein discussed MRSA and its infections in Krasnoyarsk, Siberian Russia between 2007 and 2011. The incidence of MRSA in 3,662 subjects was 22.0% and 2.9% for healthcare- and community-associated MRSA (HA- and CA-MRSA), respectively. The 15-day mortality rates for MRSA hospital- and community-acquired pneumonia (HAP and CAP) were 6.5% and 50%, respectively. MRSA CAP cases included pediatric deaths; of the MRSA pneumonia episodes available, ≥27.3% were associated with bacteremia. Most cases of HA-MRSA examined exhibited ST239/<i>spa</i>3(t037)/SCC<i>mec</i>III.1.1.2 (designated as ST239_Kras), while all CA-MRSA cases examined were ST8/<i>spa</i>1(t008)/SCC<i>mec</i>IV.3.1.1(IVc) (designated as ST8_Kras). ST239_Kras and ST8_Kras strongly expressed cytolytic peptide (phenol-soluble modulin α, PSMα; and δ-hemolysin, Hld) genes, similar to CA-MRSA. ST239_Kras pneumonia may have been attributed to a unique set of multiple virulence factors (MVFs): toxic shock syndrome toxin-1 (TSST-1), elevated PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8_Kras, SEA was included in MVFs, some of which were common to ST239_Kras. The ST239_Kras (strain OC3) genome contained: a completely unique phage, φSa7-like (W), with no <i>att</i> repetition; <i>S</i>. <i>aureus</i> pathogenicity island SaPI2R, the first TSST-1 gene-positive (<i>tst</i>⁺) SaPI in the ST239 lineage; and a super copy of IS<i>256</i> (≥22 copies/genome). ST239_Kras carried the Brazilian SCC<i>mec</i>III.1.1.2 and United Kingdom-type <i>tst</i>. ST239_Kras and ST8_Kras were MDR, with the same levofloxacin resistance mutations; small, but transmissible chloramphenicol resistance plasmids spread widely enough to not be ignored. These results suggest that novel MDR and MVF⁺ HA- and CA-MRSA (ST239_Kras and ST8_Kras) emerged in Siberian Russia (Krasnoyarsk) associated with fatal pneumonia, and also with ST239_Kras, a new (Siberian Russian) clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR.</p>