Volumen 59 (2020): Heft 3 (January 2020)

In 2019, a new human pandemic coronavirus (SARS-CoV-2) emerged in Wuhan, China. We present the knowledge about SARS-CoV-2 compared to SARS-CoV and MERS-CoV. The SARS-CoV-2 is similar to other coronaviruses, nevertheless, differences were observed. Cell entry of SARS-CoV-2 is facilitated by cleavage of spike protein by furin. The receptor-binding motif of SARS-CoV-2 spike protein forms a larger binding interface and more contacts with host receptor ACE2 compared those of in SARS-CoV. Unlike other coronaviruses, the SARS-CoV-2 spike protein has a motif, known to bind integrins. Nucleocapsid protein and RNA-dependent RNA polymerase of SARS-CoV-2 display some structural differences compared to those of SARS-CoV as well. These features may increase the efficiency of the spread of SARS-CoV-2 and indicate the putative targets for specific antiviral therapy.

1. Taxonomy of Coronaviridae. 2. Structure of Betacoronavirus virion. 3. Genome of Betacoronavirus. 4. Proteins of Betacoronavirus. 5. Betacoronavirus replication cycle. 6. Pathogenesis of SARS-CoV-2. 6.1. Tissue and cellular pathogenesis. 6.2. Molecular basis of pathogenesis. 6.3. Immunopathological changes in COVID-19. 7. Conclusions

SARS-CoV-2, a novel pathogenic human coronavirus, emerged in December of 2019 in Wuhan (Hubei province, China). In most cases, the infection causes a mild to moderate respiratory illness. However, a undefined group of infected may develop a severe or critical illness: Coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) and many other complications. Current efforts are focused on limiting the spread of the virus in the population. COVID-19 treatments are intensively evaluated, however, 8 months since the start of the pandemic and despite hundreds of clinical trials, our knowledge of effective treatments is still poor. In this review, we present the current status of drugs and treatments used during SARS-CoV-2 infection. Host-directed and virus-directed drugs, as well as new compounds specific for SARS-CoV-2 are presented.

1. Introduction. 2. Host-directed drugs. 2.1. Antiparasitic drugs with potential for repurposing. 2.2. Host proteases inhibitors. 2.3. Endocytosis inhibitors. 2.4. Immunomodulating drugs affecting host. 3. Virus-directed drugs. 3.1. Broad-range-antiviral drugs. 3.2. Inhibitors of viral S glycoprotein. 3.3. New potential virus-directed drugs against SARS-CoV-2. 4. Conclusions

Severe acute respiratory syndrome coronavirus is a new infectious disease caused by a novel coronavirus (SARS-CoV-2). In February 2020 WHO renamed the disease to coronavirus disease 2019 (COVID-19). Coronaviruses belong to the family of Coronaviridae, order Nidovirales. Scientists have visualized the appearance of the SARS-CoV-2 using microscopic techniques, which has a crown-like shape and contains four structural proteins – S, E, M and N. ACE2 (angiotensin converting enzyme 2) is a receptor to which SARS-CoV-2 virus particles bind. The primary test to diagnose infection is the RT-PCR (Real time RT-PCR). Research is underway to identify vaccine against SARS-CoV-2 and therapeutic treatments for COVID-19.

1. Introduction. 2. Epidemiology and pathogenesis of the disease. 3. Molecular structure, division and origin of coronaviruses. 4. Coronavirus binding receptors. 5. Ways of transferring infection. 6. Symptoms and course of infection. 7. Preventive recommendations. 8. Characteristics of tests used to diagnose infections caused by SARS-CoV-2 coronavirus. 9. Studies on a vaccine against SARS-CoV-2 virus. 10. COVID-19 – treatment guidelines – seeking new therapies. 11. Summary

During pregnancy many agents can be teratogenic i.e. can be dangerous for embryo or fetus and cause differentiated adverse effects. Teratogenic agents include substances (e.g. many pharmaceuticals, mycotoxins – e.g. aflatoxins and ochratoxin A), radiation (e.g. X/RTG, γ) and infectious agents. The latter include bacteria (e.g. Listeria monocytogenes, Treponema pallidum), protozoa (e.g. Toxoplasma gondii) and viruses (e.g. ZIKV, parvovirus B19, herpesviruses: CMV, HSV, VZV). Quite a few pathogens can be vertically transmitted, i.e. through placenta (poorly understood mechanism), but not all are typical teratogenic agents (TORCH group). Infection during gestation can be oligosymptomatic or asymptomatic for the mother, nevertheless can also be fatal for the child, causing among others IUGR, SNHL, malformation (e.g. microcephaly, limb defects), abortion. Some (but not all) of these abnormalities can be non-invasively diagnosed by ultrasonography (USG) and prevented by vaccination (in case of the rubella and varicella). In some countries routine serological diagnostics for selected pathogens are performed during pregnancy. Generally transplacental transmission occur mostly during initial (primary) infection and are most dangerous during the first and second trimester (intensive morphogenesis and organogenesis). Conversely chance of fetus infection usually increases with time and is highest in the third trimester.

1. Introduction. 2. Placenta. 3. Preterm delivery and vaginosis. 4. TORCH group. 5. Teratogenic microorganisms and viruses. 5.1. Bacteria. 5.2. Protozoa. 5.3. Viruses. 6. Mycotoxins. 6.1. Description of selected mycotoxins. 7. Summary

Antimicrobial resistance (AMR) is considered as one of the most important threats for public health with global dimensions. The aim of this paper is to analyze the causes and consequences of antimicrobial resistance and the actions which should be taken in order to reduce this threat. Overuse and misuse of antibiotics are believed to be responsible for the emergence of resistant pathogens. These occur not only in human medicine but also in veterinary medicine, animal husbandry and plant production. Another factor which contributes to the global spread of resistant pathogens is low sanitation, mainly encountered in low and middle income countries. However, low quality infection control programs and the lack of antibiotic stewardship programs also contribute to the dissemination of resistant strains. Other factors which were shown to have impact are population movement, medical tourism, intensive trade exchange and climate change. The consequences of increased resistance such as medical, microbiological, epidemiological, psychological and economic are also discussed. Finally, several documents of WHO and European Union underlying “One health” approach in the combat of resistance as well as international projects addressing problem of AMR are described. The importance of broad education campaigns targeting medical professionals, health care decision makers and general public in combat of AMR such as European Antibiotic Awareness Day (EU) and International Antibiotics Awareness Week (WHO) are also discussed.

1. Introduction 2. The epidemiological situation of resistance in Poland in comparison with EU countries 3. Causes of the rise and dissemination of antibiotic resistance. 4. Consequences of increasing AMR. 5. What actions have been taken in the fight against antibiotic resistance and what are their results. 6. Summary

Two-component signal transduction systems composed of histidine sensor kinase and response regulator are involved in adaptive response of pathogenic bacteria to environmental signals by regulating gene expression involved in many physiological processes, bacterial virulence, and antibiotic resistance (antibacterial compounds). Antibiotic resistance of pathogenic bacteria is one of the most important public health problems worldwide. The paper describes a signal transduction mechanism based on phosphotransfer, functioning in two-component systems and the mechanisms of antibiotic resistance governed by these systems. Several signal transduction pathways associated with resistance to antibacterial compounds and functioning in Pseudomonas aeruginosa, Acinetobacter baumannii, Aeromonas, Salmonella and Yersinia spp. have been characterized (PhoP-PhoQ, PmrA-PmrB, ParR-ParS, CzcR-CzcS, CopR-CopS, PprB-PprA, CbrB-CbrA, BlrA-BlrB and OmpR-EnvZ systems). Their role in modifying the bacterial cell surface, limiting the inflow or increasing the drug efflux from the cell, producing antibiotic-degrading enzymes or the biofilm formation is presented.

1. Introduction. 2. Mechanism of action of two-component regulatory systems. 2.1. Histidine sensor kinases. 2.2. Response regulators. 2.3. Signal transduction in two-component systems. 3. Mechanisms of antibiotic resistance controlled by two-component signal transduction systems. 3.1. Cell surface modification. 3.2. Regulation of drug inflow and outflow. 3.3. Regulation of the level of enzymes modifying/inactivating antibiotics. 3.4. Other alternative forms of resistance. 4. Characteristics of two-component signal transduction systems modulating resistance to antibacterial compounds in selected Gram-negative bacteria. 4.1. PhoP-PhoQ and PmrA-PmrB systems. 4.2. ParR-ParS system. 4.3. CzcR-CzcS and CopR-CopS systems. 4.4. PprB-PprA system. 4.5. CbrB-CbrA system. 4.6. BlrA-BlrB system. 4.7. OmpR-EnvZ system. 5. Summary

Our organism is colonized by trillions of symbiotic bacteria. The most numerous and varied bacterial population colonizes colon, upper respiratory airways and urogenital system. They act multidirectionally supporting our health. Symbiotic microbiota helps in acquirement of nutrients, regulates action of the immune system protecting mucosa and whole organism against pathogens, neutralizes some xenobiotics, thus acts as a preventive measure against carcinogenic mutations. This beneficial microbiota may be supported by uptake of probiotics and/or prebiotics in foods, diet supplements and drugs. They can be found in milk and dairy products, in particular fermented ones (e.g kefir, yoghurt and cheese), which contain both probiotics and prebiotics, including lactoferrin. This protein has a confirmed action promoting growth of symbiotic microbiota of intestine and urogenital tract. Such activity, associated with antimicrobial action regarding pathogenic microorganisms, restores equilibrium of microbiota within mucous membranes that effectively eliminates pathogens and inflammatory processes. Youngest children are supported by lactoferrin acquired with maternal milk. Later we can relay on our own, endogenous proteins, secreted by mucous membranes and neutrophils and supply of dairy products (not subjected to aggressive thermal processing) or diet supplements. We can find in the market the products containing lactoferrin alone, with another prebiotic, e.g inulin or oligosaccharides, and also with probiotics. Orally taken lactoferrin is effective as proved in a number of clinical studies. The protein is relatively resistant to digestion, may reach intestine, where acts on gut microbiota and local lymphoid tissue. In this way lactoferrin may enhance immunological status of our mucous system.

1. Introduction. 2. Gut microbiota. 3. Lactoferrin in gastrointestinal tract. 4. Prebiotic activity in gastrointestinal tract – in vitro tests. 5. Prebiotic activity in gastrointestinal tract – in vivo tests. 6. Lactoferrin in diet and nutritional supplements. 7. Summary

S. cerevisiae var. boulardii yeasts, historically recognized as a separate species, are now considered a subspecies of S. cerevisiae. Strains of S. cerevisiae var. boulardii are widely used for prevention and treatment of disorders of human digestive system. The use of preparations based on S. cerevisiae var. boulardii impacts the functioning of the intestinal barrier, which leads to a change in the composition of the digestive tract microbiota and alleviates intestinal epithelial defects. Despite the clinically confirmed probiotic properties of these unicellular microorganisms, the number of reports of infections in humans has been increasing. Population studies suggest that S. cerevisiae yeasts are responsible for 0.1–3.6% of all cases of mycoses in patients receiving therapy with probiotics containing S. cerevisiae var. boulardii. The presence of a central venous catheter, parenteral nutrition, immunosuppression and co-morbidities in patients are considered as factors predisposing for infection. This work summarizes the most important information on biology of S. cerevisiae var. boulardii and presents the latest epidemiological data on fungemia caused by these fungi.

1. Introduction. 2. Applications of S. cerevisiae yeasts. 3. Isolation and taxonomy of probiotic yeasts S. cerevisiae var. boulardii. 4. Probiotic features of S. cerevisiae var. boulardii. 5. S. cerevisiae var. boulardii infections. 5.1. Review of S. cerevisiae var. boulardii fungemia cases. 6. Conclusions

Monitoring of antibiotic consumption is one of the basic tools of the strategies to combat antibiotic resistance, is an integral part of the antibiotic stewardships and helps to ensure the rational antibiotic therapy. It is used to describe the structure and dynamics of antibacterials usage. The defined daily dose (DDD) methodology and ATC (anatomical, therapeutic and chemical) classification used in the monitoring programs determine the reliability of the analyzed data and enable the comparison of the antibiotic consumption between departments, centers and regions.

1. Introduction. 2. What is the monitoring and what it is used for? 3. Antimicrobial consumption methodology. 4. ATC methodology. 5. Defined daily dose (DDD). 6. Antimicrobial consumption measures. 7. Summary

The MALDI-TOF MS method is a new technique, which is being increasingly used in clinical laboratories for identification of microorganisms. The wide interest in this method has been aroused by its high accuracy, instantaneous identification results, and relatively low cost of analyses. However, the application of this technique for identification of dermatophytes poses difficulties. They are caused by the natural biological complexity of filamentous fungi, very slow growth of cultures, and frequent production of pigments. Furthermore, identification of dermatophytes with this technique is a challenge due to the lack of a clear species definition for some taxa or within certain species complexes. A review of scientific literature indicates that the reliability of identification of dermatophytes based on MALDI-TOF MS is in the range between 13.5 and 100%. This variability is determined by many critical factors associated with routine laboratory procedures, i.e. the type of culture medium, incubation time, protein extraction technique, type of device, or version of the reference spectrum library. Despite these numerous limitations, the MALDI-TOF MS method is part of the significant technical progress in mycological diagnostics and an alternative to the time-consuming and labor-intensive identification of dermatophytes based on morphological traits and DNA sequencing. Nevertheless, before the technique can be implemented into routine diagnostic tests, it is necessary to expand the reference spectra library and develop procedures for direct analysis of dermatological samples.

1. Introduction. 2. Identification of microorganisms using the MALDI-TOF MS method. 3. MALDI TOF MS in mycological identification. 4. Critical factors in identification of dermatophytes with the MALDI-TOF method. 4.1. Impact of the microbiological medium. 4.2. Impact of the incubation time. 4.3. Impact of the protein extraction procedure and preparation of the matrix. 4.4. Impact of the mass spectrometry apparatus. 4.5. Impact of the reference spectrum library. 4.6. Impact of the spectrum comparison algorithm. 4.7. Impact of taxonomic changes. 5. Prospects for the development of MALDI-TOF MS in mycological diagnostics. 6. Summary