Epidemiological Differentiation of Natural Foci of Hemorrhagic Fever With Renal Syndrome of the Republic of Bashkortostan

Мочалкин, П. А.; Mochalkin, A. P.; Степанов, Е Г; Фарвазова, Л А; Попов, Н. В.

doi:10.36233/0372-9311-2016-3-24-31

Cited by 3 publications

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“…[6][7][8][9][10][11] The first committed step in this pathway is catalyzed by an essential cytoplasmic acetyl-CoA carboxylase multienzyme complex 12 (see also Supporting Information Text S1), and inhibitors of the BC active site of this complex have shown antibacterial activity against several Gram-negative species. 5,[13][14][15][16][17] The BC active site is highly conserved across a number of bacterial pathogens, including P. aeruginosa, E. coli, and H. influenzae. 18 While 1 lacks the potency to become a therapeutic agent, it is a promising starting point for medicinal chemistry efforts because of its selective on-target activity, low molecular weight, and available co-crystal structures with BC that enable structure-based molecular design.…”

Section: Introductionmentioning

confidence: 99%

Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase

Andrews¹,

Kane²,

Dozzo³

et al. 2019

J. Med. Chem.

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A major challenge for new antibiotic discovery is predicting the physicochemical properties that enable small molecules to permeate Gram-negative bacterial membranes. We have applied physicochemical lessons from previous work to redesign and improve the antibacterial potency of pyridopyrimidine inhibitors of biotin carboxylase (BC) by up to 64-fold and 16-fold against E. coli and P. aeruginosa, respectively. Antibacterial and enzyme potency assessments in the presence of an outer membrane permeabilizing agent or in efflux-compromised strains indicate that penetration and efflux properties of many redesigned BC inhibitors could be improved to various extents. Spontaneous resistance to the improved pyridopyrimidine inhibitors in P. aeruginosa occurs at very low frequencies between 10 −8 to 10 −9. However, resistant isolates had alarmingly high MIC shifts (16 to >128-fold) compared to the parent strain. Whole genome sequencing of resistant isolates revealed that either BC target mutations or efflux pump overexpression can lead to the development of high-level resistance.

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Section: Introductionmentioning

confidence: 99%

Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase

Andrews¹,

Kane²,

Dozzo³

et al. 2019

J. Med. Chem.

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Spatial Features of HFRS Morbidity in Territory of Republic Bashkortostan in 2010 - 2015

Мочалкин¹,

Mochalkin²,

Степанов³

et al. 2017

Epidemiology and Vaccine Prevention

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Introduction. The main aim of the study is to identify the territories in the Republic of Bashkortostan and the categories of residents at high risk of HFRS infection for determining the directions of preventive measures. Materials and methods. Analyzed and synthesized have been the long-term data from the Service of Surveillance on Consumer' Rights Protection and Human Wellbeing Administration in the Republic of Bashkortostan on the HFRS incidence in 54 administrative districts. Results and discussion. Identified have been administrative districts with high, medium, and low risk of exposure to HFRS during. It is established that 85.2% of infections, registered at that time in Bashkortostan, occurred in the natural HFRS focus in the forest-steppe landscape-geographical zone. The urban/rural differential ratio in the natural foci in the forest-steppe area was 61.2% and 38.8%, respectively; in the forest zone-19.2% and 80.8%; while in the steppe-2.2% and 97.8%. Conclusions. In order to decrease the level of HFRS morbidity in the territory of Bashkortostan, it is necessary to considerably expand the scope and augment the intensity of preventive activities in the areas of high risk of exposure, first and foremost, in Ufa city and Ufa Region, Tuimazinsky region (Oktyarsky and Tuimazy cities), Kumertau, Birsk, and Sterlitamak cities.

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Factors Responsible for Cluster HFRS Morbidity During Winter Season in the Territory of the Republic of Bashkortostan

Мочалкин¹,

Mochalkin²,

Степанов

et al. 2018

Journal of microbiology, epidemiology and immunobiology

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Aim. Of the study was to specify the factors responsible for outbreaks of domestic cluster HFRS morbidity during winter period in the Republic of Bashkortostan as the basis for preventive measures substantiation. Materials and methods. Analyzed have been the data from the Rospotrebnadzor Administration in the Republic of Bashkortostan (RB) on the HFRS incidence in 54 administrative districts of RB during winter season 2016-2017. Summarized have been the results of epidemic foci eradication with domestic HFRS morbidity during winter months of 2010-2017 in the territory of RB. Results. Winter sporadic HFRS incidence is registered annually among the rural and urban population residing in steppe, forest-steppe and forest zones of RB. It is outlined that epidemic foci with domestic cluster HFRS morbidity emerge more frequently in the territory of forest-steppe zone. It is established that HFRS infections of domestic type take place in residential areas adjacent to some forestry to one extent or another, as well as on visiting country, out-of-town objects situated in the territory of active natural HFRS foci. Thereat, the risks of domestic HFRS infection are entirely defined by the sanitary-hygienic state of accommodation and manufacturing facilities. Conclusion. The main tactical option for the prevention of epidemic foci emergence with domestic cluster HFRS morbidity among rural and urban population of RB is simultaneous barrier and semi-rural deratization and disinfection in areas of high risk of infection.

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Epidemiological Differentiation of Natural Foci of Hemorrhagic Fever With Renal Syndrome of the Republic of Bashkortostan

Cited by 3 publications

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Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase

Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase

Spatial Features of HFRS Morbidity in Territory of Republic Bashkortostan in 2010 - 2015

Factors Responsible for Cluster HFRS Morbidity During Winter Season in the Territory of the Republic of Bashkortostan

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