Marek Fol

Publications of Marek Fol

• Interaction of Helicobacter pylori with C-Type Lectin Dendritic Cell-Specific ICAM Grabbing Nonintegrin.

  Authors: Eliza Miszczyk, Karolina Rudnicka, Anthony P Moran, Marek Fol, Magdalena Kowalewicz-Kulbat, Magdalena Druszczyńska, Agnieszka Matusiak, Maria Walencka, Wiesława Rudnicka, Magdalena Chmiela

  Journal of biomedicine & biotechnology. 01/2012; 2012:206463.

  In this study we asked whether Helicobacter pylori whole cells and lipopolysaccharide (LPS) utilize sugar moieties of Lewis (Le) antigenic determinants to interact with DC-SIGN (dendritic cellIn this study we asked whether Helicobacter pylori whole cells and lipopolysaccharide (LPS) utilize sugar moieties of Lewis (Le) antigenic determinants to interact with DC-SIGN (dendritic cell specific ICAM grabbing nonintegrin) receptor on dendritic cells (DCs). For this purpose the soluble DC-SIGN/Fc adhesion assay and the THP-1 leukemia cells with induced expression of DC-SIGN were used. We showed that the binding specificity of DC-SIGN with H. pylori Le(X/Y) positive whole cells and H. pylori LPS of Le(X/Y) type was fucose dependent, whereas in Le(XY) negative H. pylori strains and LPS preparations without Lewis determinants, this binding was galactose dependent. The binding of soluble synthetic Le(X) and Le(Y) to the DC-SIGN-like receptor on THP-1 cells was also observed. In conclusion, the Le(XY) dependent as well as independent binding of H. pylori whole cells and H. pylori LPS to DC-SIGN was described. Moreover, we demonstrated that THP-1 cells may serve as an in vitro model for the assessment of H. pylori-DC-SIGN interactions mediated by Le(X) and Le(Y) determinants.

• [Nontuberculous mycobacteria: M. marinum, M. ulcerans, M. xenopi - brief characteristics of the bacteria and diseases caused by them].

  Authors: Marek Fol, Joanna Olek, Magdalena Kowalewicz-Kulbat, Magdalena Druszczyńska, Wiesława Rudnicka

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:574-83.

  Mycobacterium is a variable group of acid-fast bacillus which contains pathogenic bacteria causing tuberculosis (MTC - Mycobacterium tuberculosis complex) and leprosy (M. leprae) as well as numerousMycobacterium is a variable group of acid-fast bacillus which contains pathogenic bacteria causing tuberculosis (MTC - Mycobacterium tuberculosis complex) and leprosy (M. leprae) as well as numerous nontuberculous mycobacteria (NTM) causing diseases mostly in people with immunodeficiency, although some NTM strains are capable of causing illnesses in non-immunocompromised patients. This group includes for example Mycobacterium marinum, Mycobacterium ulcerans and Mycobacterium xenopi. These microorganisms are environmental mycobacteria, present in developing countries of Africa, but they may also be transferred to other continents. The most common symptoms of diseases caused by these species are skin lesions (hyperpigmentation, tumors, ulcers) and arthritis. Because of the rarity of their occurrence, these mycobacteria are relatively poorly known. Effective ways of treating the diseases caused by these bacilli are still under study.

• [Recognition of mycobacterial antigens by phagocytes].

  Authors: Magdalena Druszczyńska, Marcin Włodarczyk, Marek Fol, Wiesława Rudnicka

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:28-39.

  Recognition of mycobacterial antigens by receptors of phagocytes is not only a key element of the first line of defense, but also an important link to the specific phase of the immune response. TheRecognition of mycobacterial antigens by receptors of phagocytes is not only a key element of the first line of defense, but also an important link to the specific phase of the immune response. The immune response is based on the existence of a number of pattern recognition receptors (PRR) that recognize conservative microbial structures called pathogen-associated molecular patterns (PAMP). These receptors are involved in the processes of opsonization and phagocytosis of pathogens, activation of the complement system, induction of apoptosis and signal transduction cell systems. The initiated signal cascade is supposed to lead to the mobilization of immune forces against the penetrating pathogen and is aimed at its fast elimination from the body. Understanding the role of these receptors in the antimycobacterial immune response appears to be fully justified in view of their potential application in distinguishing persons particularly sensitive to tuberculosis as well as in the development of new generation vaccines for prophylaxis and therapy and new biomarkers for improvement of the difficult and time-consuming diagnosis of mycobacterial infections.

• [Vaccination against M. tuberculosis - what next after BCG?].

  Authors: Marek Fol, Katarzyna Zawadzka, Magdalena Druszczyńska, Magdalena Kowalewicz-Kulbat, Wiesława Rudnicka

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:93-103.

  Tuberculosis (TB) still remains a huge global health problem. An increase in TB has been observed in many parts of the world, especially in poor and densely populated sub-Saharan Africa and Asia.Tuberculosis (TB) still remains a huge global health problem. An increase in TB has been observed in many parts of the world, especially in poor and densely populated sub-Saharan Africa and Asia. Tuberculosis affects not only the developing countries but also the relatively wealthy regions of Europe, particularly Eastern Europe, where drug-resistant mycobacterial strains are increasingly reported. Control of tuberculosis expansion is very difficult. It requires the long-term use of anti-mycobacterial drugs. Additionally, the HIV epidemic and the phenomenon of multi-drug resistance are assumed to be responsible for the increase in TB cases. Therefore the most reasonable form of anti-TB protection seems to be effective vaccination. At the beginning of the twentieth century the BCG vaccine was introduced into general use as the first and so far the only immune protector against tuberculosis. Now it is known that this vaccine is not powerful enough and induces protection at a relatively low level. Hence ongoing research on the development of a more powerful anti-mycobacterial vaccine is still needed. Many of the new formulations are in phase II or III of clinical trials and the results are promising. The search for new vaccines involves several strategies: modified virulence-attenuated Mycobacterium tuberculosis strains, recombination of attenuated M. bovis BCG bacilli, immunogenic mycobacterial proteins and DNA encoding selected proteins as well as unrelated microorganisms used as carriers of mycobacterial antigens. The wide range of concepts is extremely important because new vaccines should serve for immunization of the broadest possible population, not only healthy individuals but also those who are immunocompromised.

• The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides.

  Authors: Erin Maloney, Dorota Stankowska, Jian Zhang, Marek Fol, Qi-Jian Cheng, Shichun Lun, William R Bishai, Malini Rajagopalan, Delphi Chatterjee, Murty V Madiraju

  PLoS pathogens. 08/2009; 5(7):e1000534.

  The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannosideThe well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein-positive vesicles, and it exhibits altered membrane potential compared to wild type. A lysX complementing strain expressing the intact lysX gene, but not one expressing mprF alone, restored the production of L-PG and rescued the lysX mutant phenotypes, indicating that the expression of both proteins is required for LysX function. The lysX mutant also showed defective growth in mouse and guinea pig lungs and showed reduced pathology relative to wild type, indicating that LysX activity is required for full virulence. Together, our results suggest that LysX-mediated production of L-PG is necessary for the maintenance of optimal membrane integrity and for survival of the pathogen upon infection.

• Interference of Mycobacterium tuberculosis cell division by Rv2719c, a cell wall hydrolase.

  Authors: Ashwini Chauhan, Hava Lofton, Erin Maloney, Jacob Moore, Marek Fol, Murty V V S Madiraju, Malini Rajagopalan

  Molecular microbiology. 11/2006; 62(1):132-47.

  The genetic factors responsible for the regulation of cell division in Mycobacterium tuberculosis are largely unknown. We showed that exposure of M. tuberculosis to DNA damaging agents, or toThe genetic factors responsible for the regulation of cell division in Mycobacterium tuberculosis are largely unknown. We showed that exposure of M. tuberculosis to DNA damaging agents, or to cephalexin, or growth of M. tuberculosis in macrophages increased cell length and sharply elevated the expression of Rv2719c, a LexA-controlled gene. Overexpression of Rv2719c in the absence of DNA damage or of antibiotic treatment also led to filamentation and reduction in viability both in broth and in macrophages indicating a correlation between Rv2719c levels and cell division. Overproduction of Rv2719c compromised midcell localization of FtsZ rings, but had no effect on the intracellular levels of FtsZ. In vitro, the Rv2719c protein did not interfere with the GTP-dependent polymerization activity of FtsZ indicating that the effects of Rv2719c on Z-ring assembly are indirect. Rv2719c protein exhibited mycobacterial murein hydrolase activity that was localized to the N-terminal 110 amino acids. Visualization of nascent peptidoglycan (PG) synthesis zones by probing with fluoresceinated vancomycin (Van-FL) and localization of green fluorescent protein-Rv2719c fusion suggested that the Rv2719c activity is targeted to potential PG synthesis zones. We propose that Rv2719c is a potential regulator of M. tuberculosis cell division and that its levels, and possibly activities, are modulated under a variety of growth conditions including growth in vivo and during DNA damage, so that the assembly of FtsZ-rings, and therefore the cell division, can proceed in a regulated manner.

• Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator.

  Authors: Marek Fol, Ashwini Chauhan, Naveen K Nair, Erin Maloney, Meredith Moomey, Chinnaswamy Jagannath, Murty V V S Madiraju, Malini Rajagopalan

  Molecular microbiology. 06/2006; 60(3):643-57.

  Paired two-component regulatory systems consisting of a sensor kinase and a response regulator are the major means by which bacteria sense and respond to different stimuli. The role of essentialPaired two-component regulatory systems consisting of a sensor kinase and a response regulator are the major means by which bacteria sense and respond to different stimuli. The role of essential response regulator, MtrA, in Mycobacterium tuberculosis proliferation is unknown. We showed that elevating the intracellular levels of MtrA prevented M. tuberculosis from multiplying in macrophages, mice lungs and spleens, but did not affect its growth in broth. Intracellular trafficking analysis revealed that a vast majority of MtrA overproducing merodiploids were associated with lysosomal associated membrane protein (LAMP-1) positive vacuoles, indicating that intracellular growth attenuation is, in part, due to an impaired ability to block phagosome-lysosome fusion. A merodiploid strain producing elevated levels of phosphorylation-defective MtrA (MtrA(D53N)) was partially replicative in macrophages, but was attenuated in mice. Quantitative real-time PCR analyses revealed that expression of dnaA, an essential replication gene, was sharply upregulated during intramacrophage growth in the MtrA overproducer in a phosphorylation-dependent manner. Chromatin immunoprecipitation using anti-MtrA antibodies provided direct evidence that MtrA regulator binds to dnaA promoter in vivo indicating that dnaA promoter is a MtrA target. Simultaneous overexpression of mtrA regulator and its cognate mtrB kinase neither inhibited growth nor sharply increased the expression levels of dnaA in macrophages. We propose that proliferation of M. tuberculosis in vivo depends, in part, on the optimal ratio of phosphorylated to non-phosphorylated MtrA response regulator.

• Mycobacterium tuberculosis cells growing in macrophages are filamentous and deficient in FtsZ rings.

  Authors: Ashwini Chauhan, Murty V V S Madiraju, Marek Fol, Hava Lofton, Erin Maloney, Robert Reynolds, Malini Rajagopalan

  Journal of bacteriology. 04/2006; 188(5):1856-65.

  FtsZ, a bacterial homolog of tubulin, forms a structural element called the FtsZ ring (Z ring) at the predivisional midcell site and sets up a scaffold for the assembly of other cell divisionFtsZ, a bacterial homolog of tubulin, forms a structural element called the FtsZ ring (Z ring) at the predivisional midcell site and sets up a scaffold for the assembly of other cell division proteins. The genetic aspects of FtsZ-catalyzed cell division and its assembly dynamics in Mycobacterium tuberculosis are unknown. Here, with an M. tuberculosis strain containing FtsZ(TB) tagged with green fluorescent protein as the sole source of FtsZ, we examined FtsZ structures under various growth conditions. We found that midcell Z rings are present in approximately 11% of actively growing cells, suggesting that the low frequency of Z rings is reflective of their slow growth rate. Next, we showed that SRI-3072, a reported FtsZ(TB) inhibitor, disrupted Z-ring assembly and inhibited cell division and growth of M. tuberculosis. We also showed that M. tuberculosis cells grown in macrophages are filamentous and that only a small fraction had midcell Z rings. The majority of filamentous cells contained nonring, spiral-like FtsZ structures along their entire length. The levels of FtsZ in bacteria grown in macrophages or in broth were comparable, suggesting that Z-ring formation at midcell sites was compromised during intracellular growth. Our results suggest that the intraphagosomal milieu alters the expression of M. tuberculosis genes affecting Z-ring formation and thereby cell division.

• [Interleukin-18]

  Authors: Marek Fol, Teresa Gościcka

  Postȩpy higieny i medycyny doświadczalnej. 02/2003; 57(6):685-99.

  The paper describes the properties of interleukin-18 (IL-18), the cytokine originally designated as interferon-gamma inducing factor (IGIF): its production, structure and receptor (IL-18R)The paper describes the properties of interleukin-18 (IL-18), the cytokine originally designated as interferon-gamma inducing factor (IGIF): its production, structure and receptor (IL-18R) transmitting a signal to the cell. Moreover, it presents recent data on its biological activity.