Violeta Valcheva

The Stephan Angeloff Institute of Microbiology · Infectious Microbiology

In this study, we aimed to assess the activity of the essential oils from four Bulgarian oil-bearing roses Rosa damascena Mill., R. alba L., R. centifolia L., and R. gallica L., on the reference strain Mycobacterium tuberculosis H37Rv and clinical M. tuberculosis strains of the Beijing and Latin-American Mediterraneum genotypes. The chemical compos...

Tuberculosis (TB) remains a widespread infectious disease and one of the top 10 causes of death worldwide. Nevertheless, despite significant advances in the development of new drugs against tuberculosis, many therapies and preventive measures do not lead to the expected favorable health results for various reasons. The aim of this study was to eval...

Background . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal strain circulating in the Far Eastern region of Russia. Here, w...

Tuberculosis is an extremely serious problem of global public health. Its incidence is worsened by the presence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. More serious forms of drug resistance have been observed in recent years. Therefore, the discovery and/or synthesis of new potent and less toxic anti-tubercular compounds...

The aim of this study was to assess the diversity of minisatellite VNTR loci in Mycobacterium bovis/M. caprae isolates in Bulgaria and view their position within global M. bovis diversity. Forty-three M. bovis/M. caprae isolates from cattle in different farms in Bulgaria were collected in 2015–2021 and typed in 13 VNTR loci. The M. bovis and M. cap...

The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development....

Representatives of Mycobacterium tuberculosis complex (MTBC) are potential causative agents of tuberculosis in animals and humans, and Mycobacterium bovis is considered a major one among domestic and wild ruminants. In the last twenty years, the role of another representative of MTBC – Mycobacterium caprae, has been proven in the countries of Centr...

We performed synthesis of new nitrofuranyl amides and investigated their anti-TB activity and primary genetic response of mycobacteria through whole-genome sequencing (WGS) of spontaneous resistant mutants. The in vitro activity was assessed on reference strain Mycobacterium tuberculosis H37Rv. The most active compound 11 was used for in vitro sele...

The synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2‐aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM f...

Background This study aimed to characterize recent Mycobacterium bovis/M. caprae isolates from Bulgaria by whole-genome sequencing (WGS) to gain a first insight into their molecular diversity, transmission, and position within the global phylogeography of this important zoonotic species. Results The isolates were obtained from cattle in diverse lo...

Fifteen 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives 3a-d and sulfonyl hydrazones 5a-k were synthesized. They were characterized by 1H-NMR, 13C NMR, and HRMS. Mycobacterium tuberculosis strain H37Rv was used to assess their antimycobacterial activity. All compounds demonstrated significant minimum inhibitory concentrations (MIC) from 0.07...

The chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were investigated. Fifteen compounds, including triterpenoids (1, 2, 7–12), macrocyclic diterpenes of ingol type (3–6) and aromatic derivatives (13–15), were isolated by various chromatographic methods. Their structures were elucidated by a combinatio...

Lower respiratory tract infections are among the most important causes of morbidity and mortality in the pediatric population worldwide. Despite advances in treatment and prevention, childhood pneumonia is a major reason for hospital admissions and remains a leading cause of death, claiming an estimated 800,000 children’s lives in 2018. Globally, o...

Plants from the Rosacea family are rich in natural molecules with beneficial biological properties, and they are widely appreciated and used in the food industry, perfumery, and cosmetics. In this review, we are considering Rosa damascena Mill., Rosa alba L., Rosa centifolia L., and Rosa gallica L. as raw materials important for producing commercia...

Aim and objectives Despite the availability of sufficiently effective treatment regimens, prevention and control, the widespread transmission and prevalence of resistant variants of Mycobacterium tuberculosis, which do not respond to any of the commercial drugs, remains a serious health problem for both developed and developing countries. Multidrug...

Bovine tuberculosis is still a serious problem with major economic impact in many countries. The aim of study was to evaluate the diagnostic capabilities of the classical and some modern, rapid methods for isolation and identification of Mycobacterium bovis. In the period 2015-2018 from 29 outbreaks in 10 different regions of Bulgaria, 1193 lymph n...

The genus Rhizopus is a well recognized filamentous fungus, inhabiting soil, rotting fruits, vegetables, food, etc. Rhizopus arrhizus is widely used in biotechnology and is technologically important producer of organic acids and hydrolytic enzymes. The aim of this study was to estimate the capability of Rh. arrhizus KB-2 strain to produce metabolit...

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of paratuberculosis (John’s disease) mainly in large and small domestic and wild ruminants, and suspected causative agent in human Crohn’s disease. In Bulgaria, paratuberculosis is still poorly researched in both groups of ruminants. We present results of the first in-depth...

Bovine tuberculosis (bTB) represents a significant economic burden to the agriculture. In spite of decades of the control program, Mycobacterium bovis infection levels in cattle in Bulgaria continued to rise over recent years. In order to gain a better understanding of the M. bovis diversity, we used spoligotyping for strain differentiation and the...

The study reports on the synthesis and in vitro assessment of the antimycobacterial activity of a series of new indole- and indazole-based aroylhydrazones evaluated against Mycobacterium tuberculosis H37Rv. Isoniazide and ethambutol were used as reference drugs. The most active compounds 3a (MIC 0.4412 μM) and 3e (MIC 0.3969 μM) demonstrated excell...

New isoquinoline alkaloid hypepontine (1) together with a five known compounds, were identified in Hypecoum ponticum Velen, the partial synonym of Hypecoum procumbens L. The structure of the new substance was elucidated based on spectroscopic evidence. The tertiary and quaternary alkaloid mixtures as well as the isolated alkaloids were evaluated fo...

Ethionamide (ETH) plays a central role in the treatment of tuberculosis in patients resistant to the first-line drugs. The ETH, thioamide, and thiourea class of antituberculosis agents are pro-drugs that are oxidatively converted to their active S-oxides by the flavin monooxygenase EtaA of M. tuberculosis, thus initiating the chain of reactions tha...

Dichloromethane extract of propolis (DCME) originating from Pitcairn Island demonstrated potent cytotoxicity against triple-negative MDA-MB-231 human breast carcinoma cells. The results from MTT assay showed that DCME inhibits the growth of the cancer cells in a dose- and time-dependent manner and upon the cell growth inhibition propolis extract pr...

Mycobacterium tuberculosis isolates of the Beijing 94-32-cluster (also named “Central Asian/Russian Beijing strain”) constitute an important component of the population structure of the pathogen in the Former Soviet Union (FSU) countries (1-4).…

Piperine amide analogues are synthesized by replacement of the piperidine moiety with different types of cyclic amines, including adamantyl and monoterpene derived fragments. The compounds are screened for activity against Mycobacterium tuberculosis H37Rv. The most potent compounds are the 1-adamantyl and the monoterpene derived hybrids, which comb...

New 2H-chromene derivatives bearing thiazolidine-2,4-dione or hydantoin moieties were synthesized and the structures were confirmed by 1 H NMR and 13 C NMR as well as 2D NMR, FTIR and HR-ESI-MS spectra. The compounds were evaluated for their in vitro cytotoxicity against four human cancer cell lines, namely HL-60 (acute promyelocyte leukemia), REH...

A new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues 4a-e was presented. The antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and cytotoxicity against the human embryonic kidney cell line HEK-293 were teste...

This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13 M), 7o...

Mycobacterium avium subspecies paratuberculosis is the etiological agent of paratuberculosis in animals (Johne's disease) and in humans (Crohn's disease). The review summarized the etiology, epidemiology , pathogenesis and diagnosis of the disease in domestic and wild animals, and humans as well as future challenges to diagnostics, control prebioti...

The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for anti-TB activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester deriv...

Tuberculosis (TB) control remains an important public health priority for Bulgaria. The population structure of Mycobacterium tuberculosis is clonal and certain genetic families of this species (e.g., Latin-American-Mediterranean [LAM]) have attracted more attention due to their global dissemination and/or particular pathogenic properties, e.g., as...

The semiconductor zinc oxide nanomaterial (ZnO or ZnO:H) is widely used in advanced biosensor technology for the design of highly-sensitive detector elements for various applications. In the attempt to evaluate its effect on common microorganisms, two types of nanostructured transducer films have been used (average diameter 600–1000 nm). They have...

Introduction: Tuberculosis (TB) remains an important public health issue for Bulgaria. Although a number of new cases are showing a steady decline (44/100,000 in 2000, 40/100,000 in 2005), the TB incidence rate in Bulgaria is still sufficiently high (26.7/100,000 in 2013). The current population structure of Mycobacterium tuberculosis is clonal. Ce...

Summary: The present article describes the evaluation of the in vitro activity against M. tuberculosis H37Rv of eight coumarin-derived aminoalcohols and amidoamines. Seven of the compounds display activity between 10 and 20 times higher than the classicall anti-TB drug ethambutol. The combination of coumarin scaffold with aminoalcohol fragments gav...

A series of ten novel amides was designed and synthesized on the base of the camphane scaffold by coupling of isobomylamine and bomylamine with different carboxylic acids. The compounds were screened for their in vitro activity against M. tuberculosis H37Rv and cytotoxic activity against the human embryonal kidney cell line HEK-293T. Six of the str...

A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycoba...

Emergence of multidrug-resistant Mycobacterium tuberculosis strains and their global dissemination necessitate development, evaluation and comparison of the rapid molecular tests that target genetic determinants of bacterial drug resistance. A wide range of such methods is available at present and the choice of those most appropriate is among the p...

The synthesis of new enantiopure N-acyl compounds derived from (-)-fenchone has been performed. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed for most of them moderate activity. The structures bearing sulfonamide functionality have comparable activity to ethambutol and possess low cytotoxicity.

The present article describes the evaluation of the in vitro activity against M. tuberculosis H37Rv of eight coumarin-derived aminoalcohols and amidoamines. Seven of the compounds display activity between 10 and 20 times higher than the classicall anti-TB drug ethambutol. The combination of coumarin scaffold with aminoalcohol fragments gave the mos...

Three novel amido-alcohols were synthesized on the base of the camphane scaffold. Natural amino acids were transformed into their α-hydroxy analogues with retention of configuration, and attached to bornylamine. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity shifts from micromolar to...

A series of six new amidoalcohols was designed and synthesized on the base of the camphor scaffold. Natural amino acids were transformed into their α-hydroxy analogues with retention of configuration, and attached to isobornylamine. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Some of the new co...

A new isoindoline containing amino-alcohol was synthesised on the base of the camphor scaffold and evaluated for its in vitro activity against M. tuberculosis H37Rv. The compounds shows activity comparable with the one of the classical anti-TB drug ethambutol. The camphane-based structures present novel promising scaffolds for antimycobacterial age...

The synthesis of 47 structurally diverse compounds incorporating the (R)-2-amino-1-butanol motif has been realized. Ten of these compounds were found to exhibit in vitro specific activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.65 μM-14.03 μM. Five of the most active compounds 11, 22, 23, 31 and 42 (5.7-11.1 fold more active th...

BACKGROUND: Since early Neolithic, Europe as a whole and Balkans in particular were at the crossroads of human migrations thereby transmitting human pathogens across the continent. Bulgaria located near the Europe-Asia border was in the front of these migrations that left their imprint on the population structure of human pathogens circulating ther...

The local specificity of bacterial clones may be explained by long-term presence or recent importation/fast dissemination in an area. Mycobacterium tuberculosis spoligotype ST125, noticeably prevalent among Bulgaria-specific spoligotypes, has a characteristically 'abridged' profile and an uncertain clade position [Latin-American-Mediterranean (LAM)...

Here, we present results of the first study of the Mycobacterium tuberculosis genotypes circulating in Kyrgyzstan. We focused on the incarcerated population known to be at high-risk for tuberculosis (TB) and with a significant impact on TB incidence in the general population. Beijing genotype was detected in 42 of 56 M. tuberculosis sputum-extracte...

Tuberculosis remains an important public health issue for Bulgaria, a Balkan country located in the world region with contrasting epidemiological situation for tuberculosis. Here, we present results of the recent studies on the genetic diversity of Mycobacterium tuberculosis population in Bulgaria that was evaluated with various DNA fingerprinting...

Tuberculosis (TB) infects a significant proportion of the world population and constitutes a major public health problem, particularly, in the developing regions. A reemergence of TB accompanied by an increasing number of drug resistant Mycobacterium tuberculosis strains, including many resistant to multiple drugs, has been noted since the mid-1980...

A model for studying mycobacterial L-form formation in vivo was established to demonstrate the ability of M. tuberculosis to behave as a drug-tolerant L-form persister. Rats were infected by intranasal (i.n.) and intraperitoneal (i.p.) routes with 1×108 cells/ml of M. tuberculosis. At weekly intervals during a period of five weeks, samples from lun...

We report results of the first study on the molecular basis of drug resistance in Mycobacterium tuberculosis strains currently circulating in Bulgaria. The study panel consisted of 133 (including 37 drug-resistant) isolates recovered from newly diagnosed, adult pulmonary TB patients from different regions of Bulgaria in 2005--2006. Three types of t...

Clinical strains of Staphylococcus aureus with different phenotypic methicillin susceptibility characteristics, bearing or lacking the mecA gene, were tested for their ability to transform into a cell wall-deficient state under special conditions of cultivation. Conversion to L-form growth with formation of typical L-form 'fried egg' colonies and e...

Mycobacterium tuberculosis isolates from different regions of Bulgaria were studied by a variety of molecular typing tools. Based on spacer oligonucleotide typing (spoligotyping), the 113 strains were subdivided into 35 spoligotypes: 5 unique profiles and 15 profiles shared by two to 29 strains; the Hunter-Gaston diversity index (HGI) was 0.9. Comp...

The present study evaluated new markers for molecular typing of Mycobacterium tuberculosis with a collection of strains circulating in Bulgaria. A study sample included 133 strains from epidemiologically unlinked patients from different regions of the country. Spoligotyping was used as a primary typing tool; it subdivided these strains into 37 type...

The Mycobacterium tuberculosis Beijing genotype strains appear to be hypervirulent and associated with multidrug-resistant tuberculosis. Therefore, the development of a both rapid and simple method to detect the M. tuberculosis Beijing genotype is of clinical interest per se. Previously, we described a simple and fast approach to detect the Beijing...

We compared the population structure and drug resistance patterns of the Mycobacterium tuberculosis strains currently circulating in the Beijing area of China. One hundred thirteen of 123 strains belonged to the Beijing family genotypes defined by spoligotyping. The Beijing genotype strains were further subdivided into old and modern sublineages on...