Projects / Programmes
Molecular Biology of Microorganisms
January 1, 2018
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 1.06 |
Natural Sciences |
Biological sciences |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Microorganisms, microbiota, gestational diabetes, macrosomia, metagenomics, transcriptomics, bacterial metabolites, bacterial genotoxins, Escherichia coli pathogenesis, biomimetic urothelium model, antibiotic tolerance, conjugation efficiency.
Data for the last 5 years (citations for the last 10 years) on
April 23, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
267 |
8,291 |
6,931 |
25.96 |
| Scopus |
273 |
9,430 |
7,956 |
29.14 |
Researchers (13)
Organisations (1)
Abstract
The prevalence of gestational diabetes is increasing and for the mother represents a risk factor for diabetes type 2 in several years following delivery and a greater riskfor the emergence of diabetes type 2 and obesity in her child. Macrosomia, newborn weight more that 4000 g, is also on the rise in Europe and represents a greater risk for trauma in the child and mother during delivery, as well as a greater risk for obesity and diabetes type 2 during the child's adolescence and adulthood. The gut microbota plays and extremely important role in health and development. Our reseaerch will be the first to investigate the association between gut microbiota and child macrosomia. The proposed research will include metagenomic nad metatranscriptomic analysis as well as quantification of the mothers's bacterial fecal metabolites, providing holistic insight of the active microorganisms and their functions. Results of our study will be the basis for therapeutic interventions into the microbota of pregnant women, for example the use of tailored antibiotics and individualized dietary consultation, which would »in utero« prevent and treat metabolic disorders.
Bacterial genotoxins damage the host's genome and can induce tumorigenesis. It is of great concern that the prevalence of genotoxic Escherichia coli strains has been in the last years increasing. Within the framework of the research program we will investigate the factors that induce E. coli genotoxin synthesis. Insight into induction of genotoxin synthesis and of the mechanisms that protect the producer against its own toxin paves the way for developing the means to protect the host.
Perstisters are antibiotic sensitive bacteria that survive antibiotic treatment. In contrast to studies of other research groups, our previous study revealed, that persisters are metabollically active and that they survive due to the formation of an antibiotic induced protective layer of bacterial cell debris. In the proposed research we will investigate means with which to: reduce the efficiency of bacterial surface binding, enable degradation of the protective layer and increase diffusion through the protective layer to enable antibiotic activity against persisters.
We will upgrade our previous studies on natural E. coli strains with studies of pathogenesis and the discovery of novel virulence factors using the biomimetic pig urothelium model.
Conjugation, the direct transfer of DNA between bacterial cells plays a key role in the evolution of bacterial species and dissemination of antibiotic resistance genes. The proposed research program will investigate factors that affect the efficiency of conjugation to enable prevention of the dissemination of antibiotic resistance genes and to enhance the efficiency of conjugation based antimicrobial systems such as the »kill« »antikill« system prepared within the framework of our previous research program.
Significance for science
While microorganisms are the causative agents of infectious diseases they are nevertheless essential for our health and development. The human gut harbors more than 1014 microbial cells that are designated as the gut microbiota. Due to interactions with the host the gut microbiota plays an extremely important role in development and health. On the other hand, perturbations in the microbiota, dysbiosis are associated with metabolic and immune diseases including obesity and diabetes. On a global scale, the incidence of both is rising at an alarming rate, particluarly in developed countries, and both represent great threats to public heath. It is well known that an unfavorable prenatal environment, within which the fetus develops, can induce the development of chronic disease in adulthood. The incidence of gestational diabetes (GDM) is increasing and is tightly associated with the increase in the prevalence of obesity and postponing pregnancy to later years. GDM represents a risk factor for the development of diabetes type 2 within a few years following delivery as well as a higher risk for the the development of diabetes type 2 and obesity in children of mothers with GDM.
GDM is also a risk factor for delivery of a macrosomic child, birth weight more than 4000 g. Macrosomia represents a risk factor for the child and mother. Therefore, reducing the incidence of macrosomia is one of the main goals of health care during pregnancy.
We postulated that the gut microbiota exerts a significant affect on the occurence of macrosomia. Our study will be the first to investigate the microbiota and microbiota metabolites of pregnant women with GDM in association with the mothers body weight and child macrosomia.
Novel findings reveal that bacteria besides classical infections also play a significant role in chronic, autoimmune diseases and cancer. On a global scale chronic infections are responsible for approximately 25% of cancer diseases. Bacterial infections can provoke cancer due to an inflammatory response due to infection and or due to production of genotoxins. Inflammation and genotoxins provoke DNA damage. Our previous studies revealed that protein Usp produced by E. coli degrades DNA of human cell, reduces their viability and induces cytoskeletal rearrangements. As the nuclease activity of Usp inflicts damage to the genome, it could represent a risk factor for tumorigenesis. Within the framework of the proposed research we will study as of yet unknown mechanisms, that provoke genotoxin synthesis and mechanisms that protect the producer against its toxin.
Escherichia coli is a member of the gut microbiota, however particular strains are pathogenic and provoke various intestinal and extraintestinal infections. In developing countries diarrhoea inflicted by enterotoxigenic E. coli are among the most frequent causes of child mortality, while in developed countries particularly problematic are extraintestinal infections inflicted by extraintestinal pathogenic E. coli (urinary tract infections, sepsis, meningitis and of wounds). To study pathogenesis model systems are required that resemble conditions in vivo, must be affordable and relatively simple. Within the framework of the previous Research program we found that a biomimetic in vitro pig urothelium model was appropriate for the study of E. coli uropathogenesis. In the proposed research this biomimetic model will be employed to assess pathogenicity of a variety of uropathogenic and commensal strains. Subsequently, it will be employed for studies of known virulence factors, such as genotoxins as Usp and for identification of novel virulence factors. Discovery of novel virulence factors will enable better understanding of E. coli strain pathogenesis.
Bacterial antibiotic resistance is on a global scale one of the greatest health care problem. In addition, antibiotic sensitive bacteria can survive antibiotic treatment due to the appearance of »persisters«. It has long been assum
Significance for the country
Results of our research on gut microbiota of women with gestational diabetes will enable preparation of novel tailored therapeutic interventions, for example probiotics, to prevent and treat metabolic diseases.
Understanding mechanisms that induce genotoxin synthesis and mechanisms that protect the producer against its own toxin, will enable prevention and treatment of acute and chronic diseases as well as cancer diseases that are provoked by bacterial infections.
The persister phenomenon is a field of extremely intense research however, these are mostly focused on pathways that induce bacterial metabolic inactivity. In depth analysis of the formed protective network and metabolic activity of persisters will greatly enhance our understnding of persister formation and enable development of means to prevent their emergence.
A more detailed understanding of bacterial pathogenesis of uropathogenic E. coli will enable the development of novel approaches for treatment and prevention of infections. We will disseminate konwledge based on our results to raise public awareness on processess involving bacterial pathogenesis.
More in depth understanding of the factors affecting conjugation will be crucial for efficient use of conjugation based delivery of novel antimicrobial agents that would be effective upon antibiotic failure. We will inform the wider public on our results and thus contribute to public awareness on the significance of conjugation in natural environments and in medicine.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
