Nina Chanishvili - Academia.edu (original) (raw)

Papers by Nina Chanishvili

In contrast to the many reports of successful cases of personalized bacteriophage therapy, random... more In contrast to the many reports of successful cases of personalized bacteriophage therapy, randomized controlled trials of non-personalized bacteriophage products did not bring the expected results. Here, we present the outcomes of a retrospective, observational analysis of the first 100 consecutive cases of personalized bacteriophage therapy of difficult-to-treat infections facilitated by a Belgian consortium. The most common indications were lower respiratory tract, skin & soft tissue, and bone infections, and involved combinations of 26 bacteriophages, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. Eradication was 70% less probable when no concomitant antibiotics were used (odds-ratio = 0.3; 95% confidence interval = 0.127–0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibioti...

Mìkrobìologìâ ì bìotehnologìâ, Sep 30, 2018

To investigate microbial composition of the home-made Matsoni samples and select the bacterial cu... more To investigate microbial composition of the home-made Matsoni samples and select the bacterial cultures for further development of the standardized starter(s), challenging modern biotechnological requirements. Methods. Strain isolation and purification, culture evaluation for their catalase and urease activities, casein fermentation, galactose degradation ability, exopolysaccharide (EPS) and bacteriocin production, and lysogeny. Results. One hundred forty four lactic acid bacterial cultures were isolated from thirty five homemade Matsoni samples, collected from twenty four different settlements in Georgia during years 2013-2014. Bacterial structure of the starters showed great diversity in their composition, 3% of isolates showed casein degradation and EPS production potential, 32% were positive for galactose fermentation, 19% showed urease activity, 17% revealed antagonistic properties and 14% were denoted as lysogenic. Conclusions. The developed strain collection shows potential to provide various organoleptic properties to the end products and, thus, after molecular characterization, can be easily used for construction of new standardized Matsoni starters.

The idea to use living microorganisms for disease prevention and treatment was introduced a centu... more The idea to use living microorganisms for disease prevention and treatment was introduced a century ago, but yet the full potential and benefits of microbial therapeutics has not been entirely understood. In the light of developments of human microbiome studies, probiotics are gaining new momentum, where health benefit conferring by Lactobacillus are emerging as one of the novel approaches in the treatment and prophylactics of dysbiosis. The present review focuses on the origin and development of the probiotic's concept, mechanisms of action and anticipated use of probiotic Lactobacillus as well as of microbial therapeutics. The required regulatory frameworks associated with probiotic use and marketing are discussed.

Applied and Environmental Microbiology, Feb 1, 2006

Bacillus cereus strains that are genetically closely related to B. anthracis can display anthrax-... more Bacillus cereus strains that are genetically closely related to B. anthracis can display anthrax-like virulence traits (A. R. Hoffmaster et al., Proc. Natl. Acad. Sci. USA 101:8449-8454, 2004). Hence, approaches that rapidly identify these "near neighbors" are of great interest for the study of B. anthracis virulence mechanisms, as well as to prevent the use of such strains for B. anthracis-based bioweapon development. Here, a strategy is proposed for the identification of near neighbors of B. anthracis based on single nucleotide polymorphisms (SNP) in the 16S-23S rRNA intergenic spacer (ITS) containing tRNA genes, characteristic of B. anthracis. By using restriction site insertion-PCR (RSI-PCR) the presence of two SNP typical of B. anthracis was screened in 126 B. cereus group strains of different origin. Two B. cereus strains and one B. thuringiensis strain showed RSI-PCR profiles identical to that of B. anthracis. The sequencing of the entire ITS containing tRNA genes revealed two of the strains to be identical to B. anthracis. The strict relationship with B. anthracis was confirmed by multilocus sequence typing (MLST) of four other independent loci: cerA, plcR, AC-390, and SG-749. The relationship to B. anthracis of the three strains described by MLST was comparable and even higher to that of four B. cereus strains associated with periodontitis in humans and previously reported as the closest known strains to B. anthracis. SNP in ITS containing tRNA genes combined with RSI-PCR provide a very efficient tool for the identification of strains closely related to B. anthracis. Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are rather important microorganisms that interfere with or are related to human activities. B. anthracis is the active agent of anthrax disease (41), B. cereus causes food-borne disease syndromes associated with enterotoxin and emetic toxin (17, 27), and B. thuringiensis is an insect pathogen (39) currently used for the biological control of insects in crop protection. On the basis of genetic evidence, it has been proposed that B. anthracis, B. cereus, and B. thuringiensis belong to the same species (B. cereus sensu lato), but the status of separate species has been retained due to the remarkably different virulence phenotype (23). It has been hypothesized that B. anthracis derives from B. cereus-B. thuringiensis by the acquisition of the virulence pXO plasmids (29) and successive genome adaptation (30). It is thus predictable that B. cereus-B. thuringiensis strains exist that are genetically and phylogenetically closely related to B. anthracis. Several studies have shown that certain B. cereus strains are strictly related to B. anthracis. By means of amplified fragment length polymorphism (AFLP) typing, Radnedge et al. (34) individuated B. cereus and B. thuringiensis strains closely related to B. anthracis, and then tried to identify by suppression subtractive hybridization genomic regions of B.

European Urology Supplements, Mar 1, 2019

Urinary tract infections (UTIs) are among the most widespread microbial diseases and their econom... more Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥10 4 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option.

Mìkrobìologìâ ì bìotehnologìâ, Mar 15, 2008

Mìkrobìologìâ ì bìotehnologìâ, Jun 15, 2007

Виêîðисòаííÿ êуëьòуðи êë³òиí Нåð-2 у ëîãаðифм³чí³й ³ сòац³îíаðí³й фаз³ ðîсòу дëÿ пîпåðåдíьîї сêðи... more Виêîðисòаííÿ êуëьòуðи êë³òиí Нåð-2 у ëîãаðифм³чí³й ³ сòац³îíаðí³й фаз³ ðîсòу дëÿ пîпåðåдíьîї сêðиí³íãîвîї îц³íêи áåзпåêи засòîсуваííÿ аêòивíîãî фаãа Clostridium perfringens у мåдичí³й пðаêòиц³ дîзвîëиëî всòаíîвиòи сëаáêî виðажåíу циòîòîêсичíу д³ю пðåпаðаòа в êîíцåíòðац³ї 10 6 фаãîвиõ часòîê у îдíîму м³ë³ë³òð³, щî ðåєсòðуваëасÿ чåðåз 24 ãîд åêспîзиц³ї. К ë ю ч î в ³ с ë î в а : áаêòåð³îфаã, Clostridium perfringens, êуëьòуðа êë³òиí Нåð-2, циòîòîêсичí³ вëасòивîсò³.

Journal of Applied Microbiology, May 9, 2019

Aims This paper presents the potential of environmentally-sourced bacteriophages to affect the gr... more Aims This paper presents the potential of environmentally-sourced bacteriophages to affect the growth of clinical isolates of Pseudomonas aeruginosa biofilms, and assesses the respective plaque morphotypes presented by each bacteriophage, in vitro. Methods and Results Bacterial host strains were typed for their ability to produce the quorum sensing-controlled virulence factor pyocyanin, and then tested for bacteriophage susceptibility using the spot test method. The bacteriophages were co-administered with ciprofloxacin in order to determine whether the bacteriophages would demonstrate synergistic or antagonistic behaviour to the antibiotic in vitro. Results suggest a potential relationship between the bacteriophage plaque size and biofilm inhibition, where those producing smaller plaques appear to be more effective at reducing bacterial biofilm formation. Conclusions This phenomenon may be explained by a high adsorption rate leading to the rapid formation of smaller plaques, and greater biofilm reduction associated with the loss of viable bacterial cells before the cells can adhere to the surface and form a biofilm. Results from the coadministration of bacteriophage & ciprofloxacin suggest that the two work synergistically to affect P. aeruginosa biofilms. Significance and Impact of Study The data indicate enhanced efficacy of ciprofloxacin by ≥50%. This could offer an alternative strategy for targeting antibiotic-resistant infections.

Social Science Research Network, 2020

lower epigastric artery was performed in one stage with a stage of allocation of vessels on a pen... more lower epigastric artery was performed in one stage with a stage of allocation of vessels on a penis. All patients in the postoperative period accepted PDE-5 inhibitor in small doses. In the postoperative period studied frequency intra-and postoperative complications, duration of stay of the patient in a hospital, rehabilitation terms. Results: Duration of operation of 84.3 (63-110) min. Intraoperatsiony and early postoperative complications at the studied patients it was not registered, in all cases anastomosis functioned "adequately", for 1 day spontaneous adequate erections at 9 patients, at 6 patients for the 2nd day were noted. Patients were written out on average for the 5th day. Restriction of physical activities, sports activities at patients-14 days. During observation, at the operated patients, cases of a recurrence of ED were not recorded. Conclusions: When carrying out revascularization the method offered by us, at patients notes reduction of terms of an operative measure, due to simultaneous work of two teams of surgeons, rehabilitation term without loss of efficiency of intervention, the minimum cosmetic defect decreases. Also due to antegrade imposing of an anastomosis, fibrinferments of an anastomosis it was not recorded.

Current Drug Delivery, May 20, 2016

Bacteriophage (from 'bacteria' and Greek φαγεῖν phagein "to devour" or bacteria... more Bacteriophage (from 'bacteria' and Greek φαγεῖν phagein "to devour" or bacterial eaters) are bacterial viruses that infect and kill bacteria. Bacteriophages (shortly "phages") are among the most common and diverse entities in the biosphere. The estimated number of phages on earth is about 1032. Bacteriophages are often isolated from environmental sources, such as water samples, etc. Felix d'Herelle, one of the discoverers of bacteriophages, was the one who suggested them for therapy of human and animal bacterial infections. This idea was very popular in the world until the advent of antibiotics commercial after which production of therapeutic phages ceased in most of the Western countries, but not in the former Soviet Union. The application of antibiotics in the clinical practice, besides the well-known side effects, entails, in addition, the appearance of the forms of bacteria, resistant to newly synthesized preparations. It was concluded that a European and global strategy to address this gap is urgently needed. Now, faced with the alarming growth of a variety of antibiotic resistant bacterial infections, Western researchers and governments are giving phages a serious look. The phages nowadays are seen as a possible therapy against multi-drug-resistant strains of many bacteria. The therapeutic action of bacteriophages significantly differs from antibiotics, which makes them still active against multi-drug-resistant bacteria. Bacteriophages have a number of other advantages in comparison with antibiotics. First of all, they are efficient against multi-drug-resistant bacteria. The aim of this review was to provide an overview of the past and current experiences in the field of phage therapy in the countries where it has been traditionally applied in the clinical practice. Although the style and quality of old Soviet scientific publications dedicated to phage therapy are not challenging the international standards, there is still valuable information which may not be neglected by modern researchers. This information is especially important as it remained unavailable for the Western scientists before because of the language barriers until now. The goal of this article is to encourage further research on this topic, and facilitate rapid decisions on the development of appropriate regulations, which would ultimately permit the use of phages as therapeutic or preventative medicines in daily clinical practice in the Western countries where multiplying drug-resistant bacteria gradually becomes the greatest life threatening problem.

International Journal of Infectious Diseases, Aug 1, 2018

Applied and Environmental Microbiology, Aug 1, 2006

Journal of General Virology

Bacteriophages represent the most extensive group of viruses within the human virome and have a s... more Bacteriophages represent the most extensive group of viruses within the human virome and have a significant impact on general health and well-being by regulating bacterial population dynamics. Staphylococcus aureus , found in the anterior nostrils, throat and skin, is an opportunistic pathobiont that can cause a wide range of diseases, from chronic inflammation to severe and acute infections. In this study, we developed a human cell-based homeostasis model between a clinically isolated strain of S. aureus 141 and active phages for this strain (PYOSa141) isolated from the commercial Pyophage cocktail (PYO). The cocktail is produced by Eliava BioPreparations Ltd. (Tbilisi, Georgia) and is used as an add-on therapy for bacterial infections, mainly in Georgia. The triptych interaction model was evaluated by time-dependent analysis of cell death and inflammatory response of the nasal and bronchial epithelial cells. Inflammatory mediators (IL-8, CCL5/RANTES, IL-6 and IL-1β) in the culture...

Georgian medical news, 2018

B.fragilis is an obligate anaerobic commensal colonizing human intestines and carries number of p... more B.fragilis is an obligate anaerobic commensal colonizing human intestines and carries number of physiological functions. At the same time B.fragilis is commonly isolated from the septic clinical samples and due to its capsule represents one of the provoking agents for abscess development. Enterotoxigenic B.fragilis (ETBF) strains also increase the likelihood of developing colon cancer. Increasing incidence of antibiotic-resistant pathogens led to the high demand to alternative antimicrobials. Bacteriophage (phage) therapy already practiced for a century in some of the Post-Soviet countries including Georgia has been suggested as a substitute of antibiotics. It should be noted that this study is the first attempt to isolate virulent B.fragilis phages for further therapeutic application as all phages known up until now were used for detection of fecal water contamination only. The aim of the study was to isolate B.fragilis specific phages for their further use against infections cause...

Frontiers in Microbiology, 2020

A total of 291 non-duplicate isolates of non-typhoidal Salmonella (NTS) were collected from the f... more A total of 291 non-duplicate isolates of non-typhoidal Salmonella (NTS) were collected from the fecal samples of patients with salmonellosis in Armenia and Georgia during 1996–2016. The isolates were tested for resistance to antimicrobials, including extended-spectrum β-lactamases (ESBL). The high prevalence of multidrug-resistance (MDR) and ESBL-producer phenotypes was detected among Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) isolates collected from patients in Armenia between 1996 and 2016. A total of 36 MDR NTS isolates were subjected to whole genome sequencing (WGS) to determine the genetic background of antimicrobial resistance (AMR) and mobile genetic elements. All ESBL-producing S. Typhimurium isolates belonged to the same sequence type (ST328). The ESBL-producer phenotype was associated with plasmid-encoded CTX-M-5 production. A range of other plasmids was associated with resistance to other antimicrobials, including the MDR phenotype.

Annals of Agrarian Science, 2016

Lactic acid bacteria (LAB) symbionts of honeybees are certainly playing key roles in their host's... more Lactic acid bacteria (LAB) symbionts of honeybees are certainly playing key roles in their host's colony functioning. The defense against bacterial pathogen invasion by endogenous LAB has been considered as promising and usable phenomenon. This study addresses bacteriocinogeny as one of antibacterial action mode displayed by bacteria. The honeybee endogenous LAB isolated from worker honeybee intestines (61 strains), queen honeybee intestines (16 strains) and beebread (25 strains) were tested for bacteriocin production ability. We checked also well characterized bacteriocin producing LAB strains against bacteria causing American foulbrood (AFB) e Paenibacillus larvae aiming possible use of exogenous LAB for control AFB in honeybees and in the same time to observe the vulnerability of endogenous bacteria exposed to bacteriocin producers. We demonstrated that none of 102 studied LAB strains, isolated from worker honeybee intestines, from queen honeybee intestines and from beebread, produced bacteriocins detectable by the well diffusion method (WDM). All of them failed to inhibit two strains of P. larvae. Three exogenous bacteriocin-producing LAB strains were tested against the same pathogens and against 25 endogenous bacterial isolates representing 11 different LAB species. The screening showed that all the tested exogenous bacteriocin-producing strains inhibited the tested P. larvae strains. The endogenous LAB strains exhibited varied sensitivity profiles when treated with bacteriocin-producing strains. This raises similar challenges to those observed in antibiotic applications leading to dysbacteriosis, even though the efficacy of these bacteriocins against P. larvae in an in vitro system is evident.