Laboratory of Medical Microbiology

About

Introduction

Research in the Laboratory of Medical Microbiology (LMM) is centered mainly on mechanisms by which the human gastric bacteria Helicobacter pylori, manifests its pathogenicrole.H. pylori isa Gram-negative, microaerophilic, mobile, spiral bacterium which is an etiologic factor for the development of chronic gastritis and gastric or duodenal ulcer and a major risk factor for the development of gastric adenocarcinoma (class 1 carcinogen, WHO). More specifically research is focused on the study on a cellular and molecular level of mechanisms relating to induction of inflammation and progression to carcinogenesis in the gastric epithelium following chronic infection with H. pylori.

 

Topics under consideration include:

  • The correlation of putative H. pylori virulence factors to the clinical and histological condition in symptomatic carriers of the infection.
  • The pathogenic role of the H. pylori CagA virulence factor in the deregulation of intracellular cell signaling with respect to the EPIYA phosphorylation motifs-associated signaling.
  • Induction of pro-inflammatory chemokine signaling in the early stages of H. pylori infection focusing on the mechanisms involving H. pylori virulence factors
  • Anti-inflammatory activity of probiotic lactobacilli on H. pylori-induced gastritis
  • Maintenance of H. pylori Biobank which includes clinical isolates and the associated biopsies, from symptomatic patients. Isolates are fully characterized with respect to the genotype and the functional status of virulence factors (contribution to the BBMRI project).

We employ biochemical and molecular biology techniques to study H. pylori infection with clinical and laboratory-adapted and/or mutated strains on in vitro gastric epithelial cell lines and in vivo animal models, such as the H. pylori Sydney Strain 1 infecting C57BL6 mice. This animal model can be further utilized for efficacy studies with respect to antimicrobial or anti-inflammatory activities of novel antibiotic compounds.

 

Diagnostic Services offered through the HPI diagnostic dept.

  • Isolation of clinical H. pylori strains from human gastric biopsies and antimicrobial susceptibility testing

 

Public Health Services. In collaboration with major gastroenterology clinics and hospitals in Athens, we participate in the laboratory surveillance of H. pylori antibiotic susceptibility. Our laboratory is the sole National Reference Center for H. pylori infections in Greece and has participated in all the National and European studies for the determination of antibiotic susceptibility in adults and children.

Other research collaborations relating to H. pylori

  • Assessment of anti-H. pylori and anti-inflammatory activity of new drugs and natural products utilizing the in vivo infection model. Collaboration with pharmaceutical companies (Lavipharm)
  • Structural analysis of the lipo-polysaccharide (LPS) of H. pylori clinical isolates from children with the aim to develop vaccines based on LPS. Collaboration with the Institute for Biological Sciences, National Research Council, Canada)
  • Study of the putative immuno-modulating properties of H. pylori in the Experimental Autoimmune Encephalitis mouse model. Collaboration with the Medical School of the Aristotelian University of Thessaloniki.

 

Other scientific and research collaborations

The LMM collaborates closely with the Reference Laboratories of the Hellenic Pasteur Institute for the molecular phylogenetic analysis and epidemiology of viral infections. More specifically:

 

  • Measles and Rubella. Determination and phylogenetic analysis of measles during the 2005-6 measles epidemic in Greece.

 

  • Enteroviruses Laboratory investigation and phylogenetic analysis of enteroviruses involved in an aseptic meningitis outbreak in Greece during the summer of 2007.

 

  • Respiratory viruses, Influenza. Laboratory surveillance of altered resistance to oseltamivir and/or antigenic virus specificity of emerging new H1N1 strains during the 2009 pandemic of influenza H1N1.  Determination of nucleotide sequences for hemagglutinin (HA) (GenBank Nos. GQ176868 GQ229381, GQ229382, GQ229383, GQ258700, GQ280274, GQ280275, GQ280276, GQ280277, GQ280278, GQ280279, GQ280280, GQ280281, GQ280282, GQ328762, GQ328766, GQ328763, GQ328764, GQ328765), neuraminidase (NA) (GQ328767, GQ328768, GQ409638, GQ409637, GQ409645, GQ409636, GQ409641, GQ409640, GQ409642, GQ409646, GQ409647, GQ409644, GQ409643, GQ409973, GQ409639) and Matrix Proteins 1&2 (GQ229384, GQ229385, GQ258701, GQ258702, GQ280270, GQ280271, GQ280272, GQ280273, GQ328769, GQ328770, GQ328771, GQ328772).

 

  • Leishmania- Study of the MON-37 zymodeme of Leishmania donovani.
Members

Staff of Medical Microbiology Laboratory

Andreas Mentis, Director of Research, ext: 816, mentis@pasteur.gr

Dionyssios Sgouras, Principal Investigator, ext: 824, sgouras@pasteur.gr

Beatriz Martinez-Gonzalez, Assistant Researcher, ext: 812, bmartinez@pasteur.gr

Konstantinos Papadakos, Post-graduate student, ext: 812,  kpapadakos@pasteur.gr

Ioanna Sougleri, Post-graduate student, ext: 812, isougleri@pasteur.gr

*Telephone No: +30 210 6478- xxx

Research programs

Research programs

Current programs

TITLE DURATION SOURCE
ERINHA- European Research Infrastructure on Highly Pathogenic Agents, FP7-INFRASTRUCTURES-2010-

2010-13

EU
ERA-NET Parasite and host genetic diversity in Helicobacter infections 2007-2010 EU
Qualitative determination of viral load in the serum of patients with chronic Hepatitis C infection 2005-2007 Schering-Plough
Quantitative determination of viral load and/or viral genotype in the serum of patients with chronic Hepatitis C infection 2005-2007 Schering-Plough

 

Past programs

  1. ACIP Etude de la fréquence de l’infection par Helicobacter pylori (Hp) des patients présentant une pathologie gastro-duodénale, de la sensibilité des souches aux antibiotiques et de la diversité de la région 3’ du gène cagA., 2007-2008, Institut Pasteur Paris
  2. CagA motogenic effects induced on gastric epithelial cells upon H. pylori infection in vitro. Study on the interaction of CagA with PLC and effect on intracellular Ca2+ levels., 2004-2006, Hellenic Pasteur Institute
  3. PROPATH  Molecular analysis and mechanistic elucidation of the functionality of pro- and prebiotics in the inhibition of pathogenic micro-organisms to combat gastrointestinal disorders and to improve human health, 2001 – 2004, EU FP5
  4. British Council Epidemiology and guidelines for the control of pathogens Campylobacter and  Salmonella in the poultry industry, 2001 – 2002, British Council
  5. PAVET – LAVIPHARM. Study of biologically active substances with potential antimicrobial and healing activity isolated from traditional plant origin,  2001 – 2003, GSRT*
  6. Development of new type of yogurt with probiotic properties – Effect on health (Program 97 DIATRO-26) Coordinator: Α. Mentis, 1999 – 2001, GSRT*
  7. European multi-center study to monitor antibiotic resistance to H pylori in children, 2000-2001, ΕU
  8. Relationship of gastric cancer to diet and H. pylori status, 1999-2001, Pasteur Institute Greece
  9. 1998 Εuropean Multicenter in vitro study on antimicrobial resistance in H. pylori, 1998-1999, ΕU
  10. Incidence of Escherichia coli virulent strains in food specimens. Detection of virulence factors.,  1998-1999, Institute Pasteur, France
  11. cagA και vacA subtypes of H. pylori clinical strains in the child population with gastritis, 1998-1999, Hellenic Ministry of Health
  12. Development of immunodiagnostic kits for antidody detection of CMV, Toxoplasma, Rubella and Helicobacter pylori.,  1998-1999, GSRT*
  13. Development of health services provided by the Diagnostic and Vaccines Quality Control Section of Hellenic Pasteur Institute to the industry,  1998-2000, GSRT*
  14. Early inhibition of sepsis: Development of methods controlling molecular mechanisms of signal transduction via tyrosine kinases and reactive oxidative substances.,  1999-2000, GSRT*
  15. Eurohepygast: Evolution of the stomach with chronic gastritis with a particular emphasis on disease markers for peptic ulcer and premalignant conditions, 1997-1999, BIOMED I (ΕU)
  16. European research network on congenital toxoplasmosis, Working group on Standardisation and quality assurance,  1997-1999, ΒIOMED Ι (ΕU)

*GSRT: General Secretariat for Research and Technology, Greek Ministry of Education

Publications

Publications of the LMM personnel (2000-2012)

1.          Mueller D, Tegtmeyer N, Brandt S, Yamaoka Y, De Poire E, Sgouras D, Wessler S, Torres J, Smolka A, Backert S: c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains. The Journal of clinical investigation 2012, 122(4):1553-1566.

2.          Melidou A, Gioula G, Pogka V, Exindari M, Moutoussi A, Sgouras D, Papadakos K, Chatzidimitriou D, Karabaxoglou D, Mentis A et al: Molecular and phylogenetic analysis of Greek measles 2010 strains. Epidemiol Infect 2012, 140(3):432-438.

3.          Gouzelou E, Haralambous C, Amro A, Mentis A, Pratlong F, Dedet JP, Votypka J, Volf P, Toz SO, Kuhls K et al: Multilocus microsatellite typing (MLMT) of strains from Turkey and Cyprus reveals a novel monophyletic L. donovani sensu lato group. PLoS neglected tropical diseases 2012, 6(2):e1507.

4.          Breurec S, Michel R, Seck A, Brisse S, Come D, Dieye FB, Garin B, Huerre M, Mbengue M, Fall C et al: Clinical relevance of cagA and vacA gene polymorphisms in Helicobacter pylori isolates from Senegalese patients. Clin Microbiol Infect 2012, 18(2):153-159.

5.          Altman E, Chandan V, Harrison BA, Panayotopoulou EG, Roma-Giannikou E, Li J, Sgouras DN: Helicobacter pylori isolates from Greek children express type 2 and type 1 Lewis and alpha1,6-glucan antigens in conjunction with a functional type IV secretion system. J Med Microbiol 2012, 61(Pt 4):559-566.

6.          Pogka V, Kossivakis A, Kalliaropoulos A, Moutousi A, Sgouras D, Panagiotopoulos T, Chrousos GP, Theodoridou M, Syriopoulou VP, Mentis AF: Respiratory viruses involved in influenza-like illness in a Greek pediatric population during the winter period of the years 2005-2008. Journal of medical virology 2011, 83(10):1841-1848.

7.          Breurec S, Guillard B, Hem S, Papadakos KS, Brisse S, Huerre M, Monchy D, Oung C, Sgouras DN, Tan TS et al: Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori strains in Cambodia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2011, 11(8):1899-1905.

8.          Roma-Giannikou E, Rοubani A, Sgouras DN, Panayiotou J, van-Vliet C, Polyzos A, Roka N, Daikos G: Endoscopic Tests for the Diagnosis of Helicobacter pylori Infection in Children: Validation of Rapid Urease Test. Helicobacter 2010, 15:227-232.

9.          Panayotopoulou EG, Sgouras DN, Papadakos KS, Petraki K, Breurec S, Michopoulos S, Mantzaris G, Papatheodoridis G, Mentis A, Archimandritis A: CagA and VacA polymorphisms are associated with distinct pathological features in H. pylori-infected adults with peptic and non-peptic ulcer disease. J Clin Microbiol 2010.

10.        Sgouras DN, Panayotopoulou EG, Papadakos K, Martinez-Gonzalez B, Roumbani A, Panayiotou J, vanVliet-Constantinidou C, Mentis AF, Roma-Giannikou E: CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children. J Clin Microbiol 2009, 47(8):2426-2434.

11.        Roma E, Panayiotou J, Pachoula J, Kafritsa Y, Constantinidou C, Mentis A, Syriopoulou V: Intrafamilial spread of Helicobacter pylori infection in Greece. J Clin Gastroenterol 2009, 43(8):711-715.

12.        Maragkoudakis PA, Papadelli M, Georgalaki M, Panayotopoulou EG, Martinez-Gonzalez B, Mentis AF, Petraki K, Sgouras DN, Tsakalidou E: In vitro and in vivo safety evaluation of the bacteriocin producer Streptococcus macedonicus ACA-DC 198. Int J Food Microbiol 2009, 133(1-2):141-147.

13.        Logotheti M, Pogka V, Horefti E, Papadakos K, Giannaki M, Pangalis A, Sgouras D, Mentis A: Laboratory investigation and phylogenetic analysis of enteroviruses involved in an aseptic meningitis outbreak in Greece during the summer of 2007. J Clin Virol 2009, 46(3):270-274.

14.        Hubschen JM, Mihneva Z, Mentis AF, Schneider F, Aboudy Y, Grossman Z, Rudich H, Kasymbekova K, Sarv I, Nedeljkovic J et al: Phylogenetic analysis of human parvovirus b19 sequences from eleven different countries confirms the predominance of genotype 1 and suggests the spread of genotype 3b. J Clin Microbiol 2009, 47(11):3735-3738.

15.        Georgaki-Angelaki H, Lycopoulou L, Stergiou N, Lazopoulou D, Paraskevakou H, Giannaki-Psinaki M, Mentis A: Membranous nephritis associated with acquired cytomegalovirus infection in a 19-month-old baby. Pediatr Nephrol 2009, 24(1):203-206.

16.        Alam MZ, Haralambous C, Kuhls K, Gouzelou E, Sgouras D, Soteriadou K, Schnur L, Pratlong F, Schonian G: The paraphyletic composition of Leishmania donovani zymodeme MON-37 revealed by multilocus microsatellite typing. Microbes Infect 2009, 11(6-7):707-715.

17.        Kremer JR, Brown KE, Jin L, Santibanez S, Shulga SV, Aboudy Y, Demchyshyna IV, Djemileva S, Echevarria JE, Featherstone DF et al: High genetic diversity of measles virus, World Health Organization European Region, 2005-2006. Emerg Infect Dis 2008, 14(1):107-114.

18.        Kokotas SN, Bolanaki E, Sgouras D, Pogka V, Logotheti M, Kossivakis A, Horefti E, Papadakos K, Mentis A: Cocirculation of genotypes D4 and D6 in Greece during the 2005 to 2006 measles epidemic. Diagn Microbiol Infect Dis 2008, 62(1):58-66.

19.        Paraschos S, Magiatis P, Mitakou S, Petraki K, Kalliaropoulos A, Maragkoudakis P, Mentis A, Sgouras D, Skaltsounis AL: In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother 2007, 51(2):551-559.

20.        Panayotopoulou EG, Sgouras DN, Papadakos K, Kalliaropoulos A, Papatheodoridis G, Mentis AF, Archimandritis AJ: Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxyl terminus of CagA protein in Helicobacter pylori clinical isolates. J Clin Microbiol 2007, 45(2):488-495.

21.        Maeda S, Mentis AF: Pathogenesis of Helicobacter pylori infection. Helicobacter 2007, 12 Suppl 1:10-14.

22.        Kyrlagkitsis I, Ladas SD, Mallass EG, Raptis S, Mentis A, Delliou E, Zizi-Serbetzoglou A, Elemenoglou I, Antonakopoulos N, Karamanolis DG: Evaluation of a conventional ELISA (Novitec) and a near patient immunochromatographic test (Stick H. pyl) for Helicobacter pylori antigen detection in stool. Hepatogastroenterology 2007, 54(75):799-802.

23.        Spala G, Panagiotopoulos T, Mavroidi N, Dedoukou X, Baka A, Tsonou P, Triantafyllou P, Mentis A, Kyriazopoulou V, Melidou A et al: A pseudo-outbreak of human A/H5N1 infections in Greece and its public health implications. Euro Surveill 2006, 11(11):263-267.

24.        Georgopoulos SD, Polymeros D, Triantafyllou K, Spiliadi C, Mentis A, Karamanolis DG, Ladas SD: Hypergastrinemia is associated with increased risk of distal colon adenomas. Digestion 2006, 74(1):42-46.

25.        Sgouras DN, Panayotopoulou EG, Martinez-Gonzalez B, Petraki K, Michopoulos S, Mentis A: Lactobacillus johnsonii La1 attenuates Helicobacter pylori-associated gastritis and reduces levels of proinflammatory chemokines in C57BL/6 mice. Clin Diagn Lab Immunol 2005, 12(12):1378-1386.

26.        Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Kalantzopoulos G, Tsakalidou E, Mentis A: In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus casei strain Shirota. Appl Environ Microbiol 2004, 70(1):518-526.

27.        Papatheodoridis GV, Papadelli D, Cholongitas E, Vassilopoulos D, Mentis A, Hadziyannis SJ: Effect of helicobacter pylori infection on the risk of upper gastrointestinal bleeding in users of nonsteroidal anti-inflammatory drugs. Am J Med 2004, 116(9):601-605.

28.        Hynes SO, Broutet N, Wadstrom T, Mikelsaar M, O’Toole PW, Telford J, Engstrand L, Kamiya S, Mentis AF, Moran AP: Phenotypic variation of Helicobacter pylori isolates from geographically distinct regions detected by lectin typing. J Clin Microbiol 2002, 40(1):227-232.

29.        Georgopoulos SD, Ladas SD, Karatapanis S, Triantafyllou K, Spiliadi C, Mentis A, Artikis V, Raptis SA: Effectiveness of two quadruple, tetracycline- or clarithromycin-containing, second-line, Helicobacter pylori eradication therapies. Aliment Pharmacol Ther 2002, 16(3):569-575.

30.        Boyanova L, Mentis A, Gubina M, Rozynek E, Gosciniak G, Kalenic S, Goral V, Kupcinskas L, Kantarceken B, Aydin A et al: The status of antimicrobial resistance of Helicobacter pylori in eastern Europe. Clin Microbiol Infect 2002, 8(7):388-396.

31.        Antsaklis A, Daskalakis G, Papantoniou N, Mentis A, Michalas S: Prenatal diagnosis of congenital toxoplasmosis. Prenat Diagn 2002, 22(12):1107-1111.

32.        Petridou E, Dalamaga M, Mentis A, Skalkidou A, Moustaki M, Karpathios T, Trichopoulos D: Evidence on the infectious etiology of childhood leukemia: the role of low herd immunity (Greece). Cancer Causes Control 2001, 12(7):645-652.

33.        Magiatis P, Spanakis D, Mitaku S, Tsitsa E, Mentis A, Harvala C: Verbalactone, a new macrocyclic dimer lactone from the roots of Verbascum undulatum with antibacterial activity. J Nat Prod 2001, 64(8):1093-1094.

34.        Kalpoutzakis E, Aligiannis N, Mentis A, Mitaku S, Charvala C: Composition of the essential oil of two Nepeta species and in vitro evaluation of their activity against Helicobacter pylori. Planta Med 2001, 67(9):880-883.

35.        Georgopoulos SD, Ladas SD, Karatapanis S, Mentis A, Spiliadi C, Artikis V, Raptis SA: Factors that may affect treatment outcome of triple Helicobacter pylori eradication thera

*GSRT: General Secretariat for Research and Technology, Greek Ministry of Education