All posts by Postępy Mikrobiologii

Charakterystyka genotoksyn CDT (cytolethal distending toxin)

Characterization of CDT (cytolethal distending toxin) genotoxins
P. Kobierecka, A. Wyszynska, E. K. Jagusztyn - Krynicka

1. Wstęp. 2. Ogólna charakterystyka CDT – operon cdt. 3. Rola podjednostek toksyny. 4. Mechanizm składania dojrzałej toksyny, struktura CDT. 5. Losy CDT w komórkach docelowych. 6. Mechanizm intoksykacji komórki przez toksyny CDT. 7. Nietypowa toksyna CDT wytwarzana przez Salmonella enterica sv. Typhimurium. 8. Podsumowanie

Abstract: The cytolethal distending toxins (CDTs) comprise a family of intracellulary acting bacterial protein genotoxins, produced by a variety of Gram-negative pathogenic bacteria, which cause DNA damage in the target cells. The DNA damage-response in the initiated cell results in the characteristic and irreversible cell cycle arrest and apoptosis in a broad range of mammalian cell cultures. Most of CDTs are AB2 toxins composed of three different subunits: CdtA and CdtC, both exhibiting a lectin-type fold, and CdtB, which is the active component of the complex, with DNase I and phosphatase activity. Although it is generally accepted that CdtA and CdtC, required for full activity of the CdtB, mediate its delivery into host cells, their precise role in the process remains poorly understood. Also the mechanism of toxin secretion and the mechanisms of cell surface binding, uptake and trafficking require further investigation. Some bacteria utilize OMVs to secrete CDTs. After internalization by dynamin-dependent endocytosis which requires the intact lipid rafts, toxin is retrograde transported through Golgi complex and the endoplasmic reticulum into the cell nuclear compartment, where CdtB exerts its toxic activity. CDTs are virulence determinants playing an important role in the pathogenesis of several bacterial diseases associated, for example, with human infections by Campylobacter jejuni, Escherichia coli and Aggregatibacter actinomycetemcomitans.
This review encompasses recent work on CDTs and focuses on the CDTs structure as well as on the molecular mechanisms of toxin uptake and cell’s intoxication. We also discuss some  controversial issues and indicate questions which still remain unanswered.

1. Introduction. 2. General characterization of CDT – cdt operon. 3. Role of CDT toxin subunits. 4. Mechanisms of mature toxin assembly, CDT tertiary structure. 5. CDT uptake into host cells. 6. Mechanism of CDT cellular intoxication. 7. Untypical CDT toxin producting by Salmonella enterica sv. Typhimurium. 8. Summary

US3 – wielofunkcyjna kinaza serynowo-treoninowa alfaherpeswirusów

US3 – a multifunctional serine-threonine kinase of alphaherpesviruses
D. Lesiak, A. Brzozowska, K. Bieńkowska-Szewczyk, A. D. Lipińska

1. Wstęp. 2. US3 a uwalnianie kapsydów z jądra komórkowego. 3. Wpływ US3 na ekspresję genów. 4. Wpływ kinazy US3 na cytoszkielet komórki. 5. Rola kinazy US3 w blokowaniu apoptozy. 6. Właściwości immunomodulacyjne białka US3. 6.1. Oddziaływanie z systemami interferonów. 6.2. Wpływ na prezentację antygenów w kontekście cząsteczek MHC klasy I i inaktywacja limfocytów T cytotoksycznych. 6.3. Redukcja ekspresji antygenów wirusowych na powierzchni komórki. 6.4. Wpływ na aktywację limfocytów NKT. 7. Inne funkcje kinazy US3. 8. Podsumowanie

Abstract: Phosphorylation by protein kinases modulates the function of target proteins by interfering with their enzymatic activity, cellular location and/or association with other proteins. Viruses have evolved complex interactions with their hosts and often mimic cellular proteins in order to usurp the cellular machinery for their own benefit, so it is not surprising that vast number of viruses encode protein kinases. Alphaherpesvirus kinase US3 is a conserved multifunctional protein, regulating the egress of viral particles, but also responsible for alterations in cell morphology resulting from the breakdown of actin stress fibers and formation of cell projections. US3 homologs control the trafficking of viral and cellular proteins and inhibit apoptosis. The current review provides an overview of the properties and functions of alphaherpesvirus US3 protein kinase orthologues.

1. Introduction. 2. US3 and the virus egress from the cell nucleus. 3. Effect of US3 on gene expression. 4. Effect of US3 on cytoskeleton. 5. Role of US3 in the blocking of apoptosis. 6. Immunomodulatory properties of US3. 6.1. Interactions with the interferon systems. 6.2. Effect on the MHC class I-restricted antigen presentation and inactivation of cytotoxic T lymphocytes. 6.3. Reduction in the cell surface expression of viral antigens. 6.4. Effect on the activation of NKT lymphocytes. 7. Other functions of US3 kinase. 8. Summary

Wirusowe zakażenia ośrodkowego układu nerwowego. Część I: Wirusy DNA

Viral infections of the central nervous system. Part I: DNA viruses
S. Rynans, S. Walter de Walthoffen, T. Dzieciątkowski, G. Młynarczyk

1. Wstęp. 2. Wirusowe zakażenia ostre OUN. 2.1. Wirusowe zapalenie opon mózgowo-rdzeniowych. 2.2 Wirusowe zapalenie opon mózgowo-rdzeniowych i mózgu. 3. Ostre zespoły poekspozycyjne. 4. Przewlekłe zakażenia wirusowe. 5. Podsumowanie

Abstract: Clinical involvement of the central nervous system (CNS) is an unusual manifestation of human viral infection. The spectrum of brain involvement and the outcome of the disease are dependent on the specific pathogen, the immunologic state of the host, and environmental factors. Most human viruses can cause serious neurological disease of the central nervous system, either during primary infection or in the course of virus reactivation from latently infected tissue. DNA viruses cause diseases of the CNS, which can be classified into three groups: acute infections, acute post-exposure syndromes and chronic diseases. This article presents current knowledge about epidemiology and clinical presentation of DNA virus infections in the central nervous system.

1. Introduction. 2. Acute viral infections of the CNS. 2.1 Viral meningitis. 2.2 Viral meningoencephalitis. 3. Acute post-exposure syndromes. 4. Chronic viral infections. 5. Summary

Wirusowe zakażenia ośrodkowego układu nerwowego. Część II: Wirusy RNA

Viral infections of the central nervous system. Part II: RNA viruses
S. Rynans, S. Walter de Walthoffen, T. Dzieciątkowski, G. Młynarczyk

1. Wstęp. 2. Wirusowe zakażenia ostre OUN. 2.1. Wirusowe zapalenie opon mózgowo-rdzeniowych. 2.2. Wirusowe zapalenie opon mózgowo-rdzeniowych i mózgu. 2.3. Wścieklizna. 2.4. Poliomyelitis. 3. Ostre zespoły poekspozycyjne. 4. Przewlekłe zakażenia wirusowe. 5. Podsumowanie

Abstract: The central nervous system (CNS) is a target for acute viral infections, as well as a reservoir of latent and persisting viruses. Virus infections of the central nervous system are an important but likely under-diagnosed cause of neurological disease in many developing countries. Infections of the CNS are commonly due to RNA viruses that have expanded their geographic range, spread from animal reservoirs or acquired new neurovirulence properties. RNA viruses cause diseases of the CNS, which can be classified into three groups: acute infections, acute post-exposure syndromes and chronic diseases. The viral infections manifest temselves with diverse clinical symptoms, which are often common tp many other diseases. This article presents current knowledge about epidemiology and clinical presentation of RNA virus infections in the central nervous system.

1. Introduction. 2. Acute viral infections of the CNS. 2.1. Viral meningitis. 2.2. Viral meningoencephalitis. 2.3. Rabies. 2.4. Poliomyelitis. 3. Acute post-exposure syndromes. 4. Chronic viral infections. 5. Summary

Udział ludzkiego cytomegalowirusa w mechanizmach karcynogenezy glejaka wielopostaciowego

The role of human cytomegalovirus in mechanisms of glioblastoma muliforme carcinogenesis
M. Wiciński, P. Sopońska, B. Brzoszczyk, B. Malinowski, A. Michalska, E. Grześk, K. Szadujkis-Szadurska, T. Kornatowski, A. Czeczuk, G. Grześk

1. Wprowadzenie. 2. Budowa HCMV. 3. Charakterystyka glejaka wielopostaciowego. 4. HCMV w etiopatogenezie glejaka wielopostaciowego. 4.1. Inicjacja nowotworzenia. 4.2. Inwazyjność. 4.3. Angiogeneza. 4.4. Immunomodulacja. 4.5. Nowe koncepcje. 5. Podsumowanie

Abstract: Human cytomegalovirus (HCMV), a common bethaherpesvirus, usually causes asymptomatic recurrentinfections in nonimmunocompetent patients. Glioblastoma multiforme is the most common primary brain tumor, which etiopathology is unknown. Numerous studies implicate the role of HCMV in the oncogenesis of glioma by modulating signaling pathways. HCMV can modify the transcription of oncogenes such as Rb, p53 and STAT3; stimulate the mobility of glioma cells; induce angiogenesis and evade host immune response. This review aims to highlight the role of HCMV in the modulation of critical signaling pathway in glioblastoma growth.

1. Introduction. 2. HCMV structure. 3. Characteristics of glioblastoma multiforme. 4. Role of HCMV in etiopathogenesis of glioblastoma multiforme. 4.1. Initiation. 4.2. Invasion. 4.3. Angiogenesis. 4.4. Immunomodulation. 4.5. New concepts. 5. Summary