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Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug-resistant nosocomial pathogen. This class of MRSA, first reported in the early 1960s and now termed healthcare-associated MRSA (HA-MRSA), was followed by a newer class of MRSA, community-associated MRSA (CA-MRSA). The unique feature of the initial CAMRSA included Panton-Valentine leukocidin (PVL), an abscess-associated toxin and also S. aureus spread factor. CA-MRSA usually causes skin and soft-tissue infections, but occasionally causes invasive infections, including (necrotizing) pneumonia, sometimes preceded by respiratory virus infections. The most successful CA-MRSA USA300 (ST8/SCCmecIVa) caused an epidemic in the United States. In Russia, we first detected PVL-positive CAMRSA (ST30/SCCmecIVc) in Vladivostok in 2006, but with no more PVL-positive MRSA isolation. However, we recently isolated four lineages of PVL-positive MRSA in Krasnoyarsk. Regarding chemotherapy against invasive MRSA infections, vancomycin still remains a gold standard, in addition to some other anti-MRSA agents such as teicoplanin, linezolid, and daptomycin. For resistance, vancomycin-resistant MRSA (VRSA) with MICs of ≥16 μg/mL appeared in patients, but cases are still limited. However, clinically, infections from strains with MICs of ≥1.5 μg/mL, even albeit with susceptible MICs (≤2 μg/mL), respond poorly to vancomycin. Some of those bacteria have been bacteriologically characterized as vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA), generally with HA-MRSA genetic backgrounds. The features of the above PVL-positive Krasnoyarsk MRSA include reduced susceptibility to vancomycin, which meets the criteria of hVISA. In this review, we discuss a possible new trend of PVL-positive hVISA, which may spread and threaten human health in community settings.

Helicobacter pylori, one of the most prevalent human pathogens, colonizes the gastric mucosa and is associated with gastric diseases, such as gastritis and peptic ulcers, and is also a bacterial risk factor for gastric cancer. Cytotoxin-associated gene A (CagA) protein, a major virulence factor of H. pylori, is phosphorylated in cells at its Glu-Pro-IIe-Tyr-Ala (EPIYA) motif and is considered to trigger gastric cancer. CagA is classified into two forms, Western CagA with EPIYA-ABC and East Asian CagA with EPIYA-ABD, with the latter associated with a high risk of developing gastric cancer. CagA causes morphological transformation of cells, yielding the “hummingbird” phenotype in AGS cells and possibly membranous pedestals in the gastric epithelium, albeit rarely. H. pylori adherence to the gastric mucosa is not yet fully understood. Here, we describe an intrafamilial infection case of H. pylori, focusing on the gastric epithelium, H. pylori adherence, and a gene mutation in a child with protein-losing gastroenteropathy (characterized by excessive loss of plasma proteins into the gastrointestinal tract). H. pylori, which also infected family members (mother and father), was genetically a single clone with the virulence genes of an East Asian type. The patient’ gastric mucosa exhibited some unique features. Endoscopy revealed the presence of protein plugs on the mucosal surface, which were immunoelectrophoretically similar to serum proteins. Electron microscopy revealed abnormal gastric epithelial cells, totally covered with the secretions or possessing small swollen structures and irregular microvilli. The patient’s H. pylori infection was characterized by frequently occurring thick pedestals, formed along adherent H. pylori. The serum protein level returned to normal and the protein plugs disappeared after the successful eradication of H. pylori, albeit with lag periods for healing. He had a mutation in the OCRL1 gene, associated with Dent disease (asymptomatic proteinuria). Thus, in the patient’s gastric mucosa, we found the abnormal gastric epithelial cells, which may be caused by an OCRL1 mutation or H. pylori, and pedestal-rich H. pylori infection, possibly caused by a higher level of action of CagA in the abnormal epithelial cells. The data suggests a novel H. pylori virulence factor associated with “excessive plasma protein release”.

Infectious complications in cancer patients are an important public health problem. The purpose of the work is microbiological monitoring of purulent complications in cancer patients for the period 2003-2015. 4209 specimens from oncological patients were examined. The bacteriological method of investigation and PCR were used. It was established that gramnegative microflora occupied one of the leading places in the occurrence of purulent complications. A significant role was played by non-fermenting gram-negative pathogens - 32.8% of the total number of clinically significant strains. The main pathogens were characterized by a high degree of resistance to antimicrobial drugs - the proportion of MDR was 23.33%, XDR - 28.33%. The main mechanism of resistance in enterobacteria was the production of beta-lactamase of extended action (81.0%) including in K.pneumoniae (87.5%), E.coli (60.0%). During the follow-up period the number of methicillin -resistant strains increased significantly: MRSA - up to 52.5%, MRSE - up to 72.0%.

Streptococcus pneumoniae, a common human pathogen, colonizes the nasopharynx and causes diseases including acute otitis media (AOM). Herein, pneumococcal serotype distributions in children before and after PCV7 vaccination and in patients with pneumococcal disease in Siberian Russia (Krasnoyarsk) are reported. Analyses included antimicrobial susceptibility testing, sequence typing (ST), pulsed field gel electrophoresis, virulence-related surface protein gene (VSG) typing with novel primers and structural analysis by scanning electron microscopy. In healthy children (HC) prior to administration of PCV7, drug-susceptible serotype23F/ST1500 was a major pneumococcal genotype. In the PCV7 trial, multidrug-resistant serotype19A/ST320 emerged in vaccinees after PCV7, exhibiting a PCV7-induced serotype replacement. Multidrug-resistant serotype19A/ST320 was evident in patients with AOM. Community-acquired pneumonia (CAP) isolates showed genetic similarities to the AOM (ST320) genotype, constituting a common non-invasive AOM-CAP group. In contrast, meningitis isolates were more divergent. Overall, 25 ST types were identified; five (20%) of which were Krasnoyarsk-native. Regarding VSGs, PI-1 (rlrA/rrgB), PI-2 (pitA/B), psrP and cbpA were present at 54.3%, 38.6%, 48.6%, and 95.7%, respectively, with two major VSG content types, PI-1- /PI-2- /psrP+ /cbpA+ and PI-1+ /PI-2+ /psrP- /cbpA+ , being found for HC and non-invasive diseases, respectively. A major clone of serotype19A/ST320 (PI-1+ /PI-2+ ) produced the longest pneumococcal wire (pilus) structures in colonies. ST1016 (PI-1- /PI-2- ) in HC had HEp-2 cell-adherent pili. These results suggest that serotype19A/ST320 and related genotypes, with the VSG content type PI-1+ /PI-2+ /psrP- /cbpA+ , emerged in vaccinees after PCV7 in Siberia, accompanying diseases in non-vaccinated children, and that some genotypes (serotypes19A/ST320 and 18/ST1016) produced novel pneumococcal structures, predicting their roles in colony formation and adherence.

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.

A series of 3D implants and filling materials prepared from powdered biodegradable polymers, polyhydroxyalkanoates (PHAs), have been designed for the purposes of reparative osteogenesis. The 3D implants are made of resorbable polymer of hydroxybutyric acid (poly-3-hydroxybutyrate, P3HB) and a composite of this polymer with hydroxyapatite (HA) (P3HB/HA). The properties of the implants were studied in vivo in a model of segmental osteotomy and compared with commercial material Bio-Oss(®). All implants containing P3HB as the main component facilitate reconstructive osteogenesis. P3HB and P3HB/HA show pronounced osteoplastic properties; their in vivo degradation is slow and corresponds to the growth of a new bone tissue, facilitating normal reparative osteogenesis. Also, powdered P3HB and P3HB/tienam can be used as filling materials for osteoplasty of bone cavities infected by Staphylococcus aureus. Biodegradable 3D implants and P3HB-based filling materials show pronounced osteoplastic properties and degrade in vivo at a slow rate, enabling normal reparative osteogenesis.