Vol 8, No 4 (2018)

Abstract. The article presents not previously published archive data and copies of documents about Lieberman Yakov Yulievich, the first director of the Petrograd Bacteriological Institute named after Pasteur (now called Saint Petersburg Pasteur Institute). Based on the personal testimony of Ya.Yu. Lieberman, Pyotr Petrovich Maslakovets and Georgii Dmitrievich Belonovsky (the founders and leaders of the Institute) preserved in the archive funds of the Directorate of the Federal Security Service (FSB) of Russian Federation for St. Petersburg and the Leningrad Region, and taking into account the Act of the Commission for the Institute Inspection from December 1930, provided in the article, the authors consistently trace the path of transformations that the Institute has undergone since its foundation. These data are illustrated by copies of publication advertisements contained in the annual city reference book "All Petersburg" for years 1910, 1911, 1912, 1914, 1923, 1924, and 1925 (from the funds of the National Library of Russia). The article also contains copies of official documents dated 1913 and 1914 and stored in the funds of the Central State Historical Archive of St. Petersburg. All documents provided establish the fact that the date of creation of the Institute is 1908.

Abstract. Pyrazinamide (PZA) is unique in that it is a component of the first line therapy for drug sensitive tuberculosis and in most current and experimental treatments also for multi drug resistant tuberculosis. Furthermore, PZA has been shown to help to ensure lasting cure and prevent relapse in shorter multi drug regimens. PZA is a prodrug. Mycobacterial tuberculosis (MTB) PncA enzyme activates the anti-mycobacterial prodrug PZA by transforming it into pyrazinoic acid (POA). The majority of clinical PZA resistant isolates contain mutations within the pncA gene and therefore remain sensitive to POA as they no longer activate PZA. Resistance to the active compound POA requires an alternative resistance mechanism and in vitro selected spontaneous MTB POA resistant mutants typically acquire a range of mutations in panD or mutations in one of a series of genes most of which are associated with the regulation of the bacterial stringent response. Clinically isolated PZA resistant MTB strains resistant to PZA and POA with mutations in any of these genes are unusual. Thus, it is likely the stringent response is critical for MTB in vivo and a damaged stringent response results in at least a reduction in fitness. Various lead compounds that disrupt the MTB stringent response have been identified that might form the basis for drugs with activity against latent mycobacteria with the potential to shorten tuberculosis treatment. Here we discuss the role of latency in the lifecycle of MTB and possible links to the activity PZA with a focus on potential new targets and drugs.

Abstract. Background. Mycobacterium avium subsp. hominissuis (MAH) is an important pathogen responsible for most of the human-associated nontuberculous mycobacteria infections. Over the past few decades the incidence of MAH infections is increasing in Italy, as in many countries worldwide. The present study is aimed to elucidate the genetic characteristics of MAH strains isolated from human patients using VNTR typing and to show the genetic relatedness among them.
Methods. The genetic diversity of 108 human isolates of MAH was determined by VNTR analysis targeting 8 loci, coded 32, 292, X3, 25, 3, 7, 10 and 47. Results. The VNTR analysis revealed 25 distinct VNTR patterns; of these, 13 patterns were unique, while 12 patterns were shared by 2 or more isolates, thus yielding 12 clusters including a total of 95 isolates. The discriminatory power of our VNTR analysis yielded an HGDI of 0.990, indicating that VNTR typing has an excellent discriminatory power. No association of a particular VNTR pattern with a particular clinical feature, such as the disseminated, pulmonary or extrapulmonary type of infection, was observed. Minimum spanning tree analysis showed that 21 VNTR patterns, occurring either as clustered or unique isolates, differed from the nearest one for one allelic variation.
Conclusions. The results obtained through the VNTR analysis showed that most MAH strains displayed a close genetic relationship. This high phylogenetic proximity of the VNTR loci over a long time period supports the concept that the MAH genotype is highly homogeneous in our geographical area, suggesting the hypothesis of the presence of possible sources of infection and transmission pathways at the local level.

Abstract. Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.

Abstract. The influenza season 2017–2018 started significantly later compared to the five previous seasons. Influenza epidemic lasted for 12 weeks (weeks 6–17), was of moderate intensity and 10,4% of the population of the country was involved with children aged 0–2 and 3–6 years being the most affected groups as usually. The average hospitalization rate of patients with ILI and ARI was 2,6% and was the highest in infants aged 0–2 years (5,4%). The number of influenzaassociated deaths was two times higher this season compared to 2016–2017 which can be attributed to the circulation of A(H1N1)pdm09 viruses that still is the major cause of lethal influenza outcomes in the country. A total 72 759 patients were investigated by RT-PCR in 55 collaborating RBLs. Laboratory confirmed influenza (LCI) was detected in 12 149 (20.7%) cases, of which 39.3% were influenza A(H1N1)pdm09 viruses, 29.6% were A(H3N2) and 31.1% influenza B (Yamagata lineage) viruses. The first cases of influenza viruses were detected at the very beginning of the season (weeks 40–45.2017), however a distinct increase in the rate of detection was registered only from the week 2.2018 with the peak on the week 13–14.2018 and subsequent gradual decline up to the end of the season. The certain differences in the etiology of morbidity between Federal Districts were registered. The impact of influenza and other ARI agents in different stage of epidemic was determined. In the pre-epidemic period, the incidence growth was occurred mainly due to ARI agents (about 32,7%), especially due to rhinoviruses (RhV) and RSV (10.2 and 8.0% cases, respectively) while LCI were registered in 3.4% only. During the epidemic, the rate of LCI detection increased up to 29.2% at simultaneous decrease in frequency of parainfluenza, adenovirus, bocavirus, coronavirus and, especially, rhinoviruses, to a lesser extent RSV infection. In the post-epidemic period, the role of influenza A(H1N1)pdm09, A(H3N2) and В viruses decreased up to 6.1; 6.9 and 3.6%, respectively, with increase of rhinoviruses (9.5% of diseases). Genetic analysis of influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in 2017–2018 season showed that all analyzed viruses by the structure of surface genes encoding antigenic determinants, in difference from influenza B viruses, corresponded to the vaccine strains recommended by WHO for the Northern Hemisphere for 2017–2018 epidemic season. However, significant changes in the internal genes of circulating viruses were revealed. The control of the susceptibility of 316 influenza A and B viruses to antiviral drugs showed that the absolute majority of them (99.7%) retained their susceptibility to neuraminidase inhibitors.

Abstract. Currently, a search for augmenting antibiotics activity is still crucial due to elevated frequency of detecting carbapenem-resistant Gran-positive bacterial isolates. To resolve this, it might be reasonable to combine carbapenems metal-â-lactamase (MâL) inhibitors. Unfortunately, no MâL inhibitors approved for treatment of carbapenem-resistant infections are currently available. Pathogenic bacteria may survive antibiotic attack, exert tolerance and persistence accompanied with the ongoing infectious process. In connection with this, determining dependence between antimicrobialrelated bactericidal effect and exposure time on microbes at 4, 8, 12 and 24 hours after the onset, a so called time-kill assay, is necessary. A synergy between both agents was noted upon reduced microbial population by ≥ 3 log10. A checkerboard array followed by seeding the microplate well contents onto a dense nutrient medium at various time points were used to assess a synergistic efficacy of carbapenems applied together with clodronic acid against MâL-producing VIMgenotype P. aeruginosa 532/14 clinical isolate obtained from patients with infectious complications (minimal inhibitory concentrations [MIC] for imipenem or meropenem were 512 μg/ml), microbial burden 106 CFU/ml. Optical density was measured at two wavelengths (490 and 630 nm) in ELx800 reader, within 4–24 hour exposure time to determine time of logarithmic growth phase emerging in test culture. It is noteworthy that magnitude of optical density is a difference between two bichromatic measurements resulting in remarkably reduced inaccuracy due to scratches or fingerprints left on the plate. It was found that clodronic acid exhibited a synergic bactericidal effect with carbapenems against a clinically resistant MâL-producing VIM-genotype P. aeruginosa 532/14 strain. Upon that, imipenem-related antimicrobial activity was evident as early as 8 hours after the onset decreasing cell growth down to 1.4 log10 compared to control, whereas 12 hours later it resulted in total inhibition of test strain by decreasing growth of the test strain by 6 log10. Meropenem in combination with clodronic acid showed a more pronounced activity: complete absence of P. aeruginosa 532/14 growth by 8 hours of incubation, growth suppression by 3.2 log10, which reached 6 log10 12–24 hours after the onset. Time-kill assay allows to identify efficient combinations of carbapenems and MâL inhibitors, which is of great importance for increasing therapeutic efficacy of patients with severe purulent-septic complications.