Medical Microbiology | Ελληνικό Ινστιτούτο Παστέρ

Laboratory of Medical Microbiology

Dionyssios Sgouras | Department of Microbiology

Research Director

Contact:

ABOUT

Research in the Laboratory of Medical Microbiology (LMM) is centered mainly on mechanisms by which the human gastric pathogen Helicobacter pylori, manifests its pathogenic role. H. pylori has been recognized as the etiologic factor for the development of chronic gastritis and peptic ulcer and the primary risk factor for the development of gastric adenocarcinoma (class 1 carcinogen, WHO).

RESEARCH PROGRAMS

Established research tools within the laboratory include:

In vitro H. pylori infection systems utilizing clinical and laboratory-adapted and/or mutated bacterial strains infecting a number of gastric epithelial cell lines (AGS, N-87, MKN45 etc.)
pylori in vivo animal models (Sydney Strain 1 and HPARE strains in C57BL6 mice), histopathological evaluation of associated gastritis by the modified Sydney System.
Biobank of pylori clinical isolates with matching gastric biopsies and blood samples from symptomatic patients (adults and children), with complete history of clinical symptoms and gastrointestinal pathology reports.
Microarray and RNAseq analysis of experimentally infected gastric epithelial cell lines infected by laboratory-adapted and/or mutated bacterial strains.

The following with relation to H. pylori are pursued:

Mechanisms of bacterial pathogenesis

Studying the role of H. pylori virulence factors CagA and VacA in the induction of pro-inflammatory response in in vitro experimental H. pylori infection of gastric epithelial cells and symptomatic patients (Papadakos et al. Helicobacter 2013; Papadakos et al. PLoS One 2013; Panayotopoulou et al. J Clin Microbiol 2007; Sgouras et al. J Clin Microbiol 2009; Panayotopoulou et al. J Clin Microbiol 2010)
Exploration of mechanisms by which H. pylori factors can promote tissue remodelling within the lamina propria, via induction of matrix metalloproteinases (MMPs). Identification and mapping of basic signalling pathways that lead to the activation of the particular MMP-specific or -related determinants (Sougleri et al. FEBS J 2015; Costa et al. J Infect Dis 2016)
Characterization of the spectrum of genomic and epigenomic variations of benign strains of H. pylori based on isolates from chronically infected individuals. Identification of molecular features that may contribute to pathologic effects by comparing the profile of benign infection to corresponding spectra of isolates from individuals with gastric cancer and premalignant lesions. Participation in the Helicobacter pylori Genome Project: understanding a bacterial carcinogen funded by the National Institutes of Health and the National Cancer Institute (NIH/NCI) intramural program 2016-2017, USA.
Participation in international collaborative research on H. pylori virulence factors (Altman et al. J Med Microbiol 2012; Bugaytsova et al. Cell Host & Microbe 2017; Mueller et al. J Clin Invest 2012

Assessment of putative anti-bacterial and anti-inflammatory activity utilizing in vitro and in vivo infection systems for identification of:

New drugs and natural products (Paraschos et al. Antimicrob Agents Chemother 2007)
Members of the gastrointestinal microbiome with probiotic properties (Sgouras et al. Applied Environmental Microbiology 2004; Sgouras et al. Clin Diagn Lab Immunol 2005)

Laboratory surveillance of H. pylori antibiotic resistance to common antibiotics utilized in the eradication schemes

Participation in prospective clinical studies for the evaluation of eradication efficiency (Georgopoulos et al. Helicobacter 2013; Georgopoulos et al. Eur J Intern Med 2016)
Monitoring antibiotic susceptibility of H. pylori on a national (Martinez-Gonzalez et al. Helicobacter 2015) and international level (Third European Multi-center study on antibiotic susceptibility of Helicobacter pylori.)

Participation of LMM staff (Dr. Mentis, Dr. Sgouras, Dr. Martinez-Gonzalez) in the team of experts in the areas of microbiology and gastroenterology, set by the Hellenic Society of Gastroenterology, responsible to reach a consensus statement on the guidelines for diagnosis, clinical management and treatment of pylori infection, in Greece.

Β. Public Health Services

During emerging epidemics and or pandemics, LMM staff provides support in the development and implementation of novel molecular diagnostic tools and appropriate standard operating procedures for the genetic characterization and the phylogenetic/phylodynamic analysis of viral, bacterial and parasitic infections. For this purpose, LMM is developing novel methods for the metagenomic determination of the composition of microbial communities, based on next generation sequencing technologies and a bioinformatics specialist has been recruited (Dr. Karamitros). In addition, members of LMM (Dr. Sgouras, Dr. Mentis) have participated through FP7-INFRASTRUCTURES-2010-1, in the preparative phase of the European Research Infrastructure for Highly Pathogenic Agents (ERINHA), pursuing the implementation of a distributed pan-European high security research infrastructure for research on suspected risk group-4 pathogens. This has provided the LMM staff with the opportunity to access expertise, capacities and functions required when coming in contact with risk group-4 and/or unknown pathogens and to obtain training in procedures working at high containment. Currently LMM is participating through ERINHA2 H2020-INFRADEV-1-2015-2 in the preparative phase of the ERINHA framework and the research portfolio.

FUNDING

CURRENT RESEARCH PROGRAMS
TITLE	DURATION	SOURCE
Vaccine Unit Restructuring-“Development of Innovative Biological products and services for infectious and neurodegenerative diseases”	2017-2020	Stavros Niarchos Foundation 810,000 €
Helicobacter pylori Genome Project: understanding a bacterial carcinogen. International collaborative project funded by the National Institutes of Health and the National Cancer Institute	2016-2017	(NIH/NCI) intramural program, USA
ERINHA2 (689622) “European Research Infrastructure on Highly Pathogenic Agents”, H2020-INFRADEV-1-2015-2.	2015-2017	EU 45,187 €
SIEMENS Hellenic Pasteur Institute Business Plan for the development of Next Generation Sequencing Technology aiming to improved diagnosis, laboratory surveillance and control of Infectious Diseases	2015-2017	GSRT 230,000 €
HHPSG National Multicenter Laboratory Surveillance Study on antibiotic susceptibility of Helicobacter pylori.	2012-2016	Hell. Soc. of Gastroenterology and the Hell. H. pylori Study Group
InfeNeuTra-2012 (MIS-450598) “Infectious and neurodegenerative diseases in the 21st Century: Basic Mechanisms to translational research for diagnosis, prevention and therapy”	2012-2015	GSRT
PAST RESEARCH PROGRAMS

TITLE	DURATION	SOURCE
CagAECM-Contribution of Helicobacter pylori CagA oncoprotein in the induction of factors involved in extracellular matrix remodeling and gastric carcinogenesis	2012-2014	Hellenic Soc. Gastrointestinal Oncology 20.000 €
ERINHA—European Research Infrastructure on Highly Pathogenic Agents, FP7-INFRASTRUCTURES-2010-1	2010-2013	EU 91.254 €
EHSG-Third European Multicentre Study on antibiotic susceptibility of Helicobacter pylori.	2008-2010.	European Helicobacter Study Group (EHSG).
ERA-NET Parasite and host genetic diversity in Helicobacter infections	2007-2010	EU 14,656 €
Qualitative determination of viral load in the serum of patients with chronic Hepatitis C infection	2005-2007	Schering-Plough 45,000 €
Quantitative determination of viral load and/or viral genotype in the serum of patients with chronic Hepatitis C infection		Schering-Plough 160,000 €
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 8,214 €
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 13,500 €
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 5^TH Framework program 264,124 €
British Council Epidemiology and guidelines for the control of pathogens Campylobacter and Salmonella in the poultry industry	2001 – 2002	British Council 4,500 €
PAVET – LAVIPHARM. Study of biologically active substances with potential antimicrobial and healing activity isolated from traditional plant origin	2001 – 2003	GSRT* 14,674 €
97 DIATRO-26-Development of new type of yogurt with probiotic properties – Effect on health	1999 – 2001	GSRT*
European multi-center study to monitor antibiotic resistance to H pylori in children	2000-2001	ΕU
Relationship of gastric cancer to diet and H. pylori status	1999-2001	Pasteur Institute Greece
1998 Εuropean Multicenter in vitro study on antimicrobial resistance in H. pylori	1998-1999	ΕU
Incidence of Escherichia coli virulent strains in food specimens. Detection of virulence factors.	1998-1999	Institute Pasteur, France
cagA και vacA subtypes of H. pylori clinical strains in the child population with gastritis	1998-1999	Hellenic Ministry of Health
Development of immunodiagnostic kits for antidody detection of CMV, Toxoplasma, Rubella and Helicobacter pylori.	1998-1999	GSRT*
Development of health services provided by the Diagnostic and Vaccines Quality Control Section of Hellenic Pasteur Institute to the industry	1998-2000	GSRT*
Early inhibition of sepsis: Development of methods controlling molecular mechanisms of signal transduction via tyrosine kinases and reactive oxidative substances.	1999-2000	GSRT*
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)
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, Ministry of Education

TRAINING

REGULATIONS

COURCES

PUBLICATIONS

Georgopoulos SD, Papastergiou V, Martinez-Gonzalez B, Xirouchakis E, Familias I, Sgouras D, Mentis A, Karatapanis S. Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial. Ann Gastroenterol. 2018 Mar-Apr; 31(2):205-210. doi: 10.20524/aog.2017.0221.

2018

Bugaytsova J, Chernov YA, Gideonsson P, Henriksson S, Mendez M, Sjöström R, Mahdavi J, Shev-tsova A, Quintana-Hayashi M, Ilver D, Moskalenko R, Aisenbrey C, Bylund G, Schmidt A, Moonens K, Björnham O, Brännström K, Königer V, Vikström S, Rakhimova L, Ögren L, Hofer A, Liu H, Goldman M, Whitmire JM, Younson JS, Kelly CG, Gilman RH, Chowdhury A, Mukhopadhyay AK, Nair BG, Papadakos KS, Martinez-Gonzalez B, Sgouras DN, Engstrand L, Unemo M, Danielsson D, Suerbaum S, Oscarson S, Morozova-Roche L, Gröbner G, Holgersson J, Esberg A, Strömberg N, Eldridge A, Chromy BA, Hansen LM, Solnick JV, Schedin S, Lindén SK, Haas R, Dubois A, Merrell DS, Remaut H, Arnqvist A, Berg DE, Borén T. (2017) Adaptation of the oncopathogen H. pylori during chronic in-fection and to gastric disease by acid responsive adherence Cell Host & Microbe. Mar 8;21(3):376-389, doi: 10.1016/j.chom.2017.02.013

2017

Georgopoulos SD, Xirouchakis E, Martinez-Gonzalez B, Zampeli E, Grivas E, Spiliadi C, Sotiropoulou M, Petraki K, Zografos K, Laoudi F, Sgouras D, Mentis A, Kasapidis P, Michopoulos S. (2016) Ran-domized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area. Eur J Intern Med. pii: S0953-6205(16)30080-2. doi: 10.1016/j.ejim.2016.04.011.

Costa AM, RM Ferreira, I Pinto-Ribeiro, IS Sougleri, MJ Oliveira, L Carreto, MA Santos, DN Sgouras, F Carneiro, M Leite and C Figueiredo (2016) Helicobacter pylori activates matrix metalloproteinase-10 in gastric epithelial cells via EGFR and ERK-mediated pathways. J Infect Dis. 213(11): 1767-76 doi: 10.1093/infdis/jiw031

2016

Sougleri IS, KS Papadakos, MP Zadik, M Mavri-Vavagianni, AF Mentis and DN Sgouras (2015) Heli-cobacter pylori CagA protein induces factors involved in the Epithelial-to–Mesenchymal-Transition (EMT) in infected gastric epithelial cells in an EPIYA- phosphorylation-dependent manner. FEBS J. 283(2): 206-220 doi: 10.1111/febs.13592

Sgouras DN, Trang TT, Yamaoka Y. (2015) Pathogenesis of Helicobacter pylori Infection. Helicobac-ter. Sep;20 Suppl 1:8-16. doi: 10.1111/hel.12251.

2015

Tropcheva R, Hristova J, Georgieva R, Salageanu A, Sgouras DN, Danova S (2013) In vitro assess-ment of prebiotic utilization by dairy lactobacilli. Bulgarian J. Agric. Sci, 19, 105-107.

Georgopoulos SD, Xirouchakis E, Martinez-Gonzalez B, Sgouras DN, Spiliadi C, Mentis AF, and Laoudi F. (2013) Clinical evaluation of a ten day regimen with Esomeprazole, Metronidazole, Amoxicil-lin, and Clarithromycin for the eradication of Helicobacter pylori in a high Clarithromycin resistance ar-ea. Helicobacter. 2013 Dec; 18(6):459-67.

Papadakos KS, Sougleri IS, Mentis AF, Hatziloukas E, Sgouras DN. (2013) Presence of Terminal EPIYA Phosphorylation Motifs in Helicobacter pylori CagA Contributes to IL-8 Secretion, Irrespective of the Number of Repeats. PLoS One 8:e56291.

Papadakos KS, Sougleri IS, Mentis AF, Sgouras DN. (2013) A Mutagenesis Method for the Addition and Deletion of Highly Repetitive DNA Regions: The Paradigm of EPIYA Motifs in the cagA Gene of Helicobacter pylori. Helicobacter; 18(3):229-41.

2013

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

Altman E, Chandan V, Harrison BA, Panayotopoulou EG, Roma-Giannikou E, Li J, Sgouras DN. (2012) Helicobacter pylori isolates from Greek children express type 2 and type 1 Lewis and alpha 1,6-glucan antigens in conjunction with a functional type IV secretion system. Journal of Medical Mi-crobiology 61:559- 566.

Boziki M, Grigoriadis N, Deretzi G, Lagoudaki R, Panayotopoulou E, Sgouras D, Mentis A, Tascos N, Kountouras J. (2012) Helicobacter pylori Immunomodulative Properties in a Mouse Model of Multiple Sclerosis. Immunogastroenterology 1: 34-39

2012

Breurec S, Michel R, Seck A, Brisse S, Come D, Dieye FB, Garin B, Huerre M, Mbengue M, Fall C, Sgouras DN, Thiberge JM, Dia D, Raymond J. (2011) Clinical relevance of cagA and vacA gene pol-ymorphisms in Helicobacter pylori isolates from Senegalese patients. Clinical Microbiology and Infec-tion 18:153-159.

Breurec S, Guillard B, Hem S, Papadakos KS, Brisse S, Huerre M, Monchy D, Oung C, Sgouras DN, Tan TS, Thiberge J-M, Vong S, Raymond J, Linz B. (2011) Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori strains in Cambodia. Infection Genetics and Evolution 11:1899-1905.

2011

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

Panayotopoulou EG, Sgouras DN, Papadakos KS, Petraki K, Breurec S, Michopoulos S, Mantzaris G, Papatheodoridis G, Mentis A, Archimandritis A. (2010) CagA and VacA Polymorphisms Are Associat-ed with Distinct Pathological Features in Helicobacter pylori-Infected Adults with Peptic Ulcer and Non-Peptic Ulcer Disease. Journal of Clinical Microbiology 48:2237-2239.

2010

Sgouras DN, Panayotopoulou EG, Papadakos K, Martinez-Gonzalez B, Roumbani A, Panayiotou J, vanVliet-Constantinidou C, Mentis AF, Roma-Giannikou E. (2009) CagA and VacA Polymorphisms Do Not Correlate with Severity of Histopathological Lesions in Helicobacter pylori-Infected Greek Children. Journal of Clinical Microbiology 47:2426-2434.

Maragkoudakis PA, Papadelli M, Georgalaki M, Panayotopoulou EG, Martinez-Gonzalez B, Mentis AF, Petraki K, Sgouras DN, Tsakalidou E. (2009) In vitro and in vivo safety evaluation of the bacteri-ocin producer Streptococcus macedonicus ACA-DC 198. International Journal of Food Microbiology 133:141-147.

Alam MZ, Haralambous C, Kuhls K, Gouzelou E, Sgouras D, Soteriadou K, Schnur L, Pratlong F, Schoenian G. (2009) The paraphyletic composition of Leishmania donovani zymodeme MON-37 re-vealed by multilocus microsatellite typing. Microbes and Infection 11:707-715.

2009

Paraschos S, Magiatis P, Mitakou S, Petraki K, Kalliaropoulos A, Maragkoudakis P, Mentis A, Sgour-as D, Skaltsounis A-L. (2007) In vitro and in vivo activities of chios mastic gum extracts and constitu-ents against Helicobacter pylori. Antimicrobial Agents and Chemotherapy 51:551-559.

Panayotopoulou EG, Sgouras DN, Papadakos K, Kalliaropoulos A, Papatheodoridis G, Mentis AF, Ar-chimandritis AJ. (2007) Strategy to characterize the number and type of repeating EPIYA phosphory-lation motifs in the carboxyl terminus of CagA protein in Helicobacter pylori clinical isolates. Journal of Clinical Microbiology 45:488-495.

2007

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

2005

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

De Vuyst L, Makras L, Avonts L, Holo H, Yi Q, Servin A, Fayol-Messaoudi D, Berger C, Zoumpopou-lou G, Tsakalidou E, Sgouras D, Martinez-Gonzales B, Panayotopoulou E, Mentis A, Smarandache D, Savu L, Thonart P, Nes I. (2004) Antimicrobial potential of probiotic or potentially probiotic lactic acid bacteria, the first results of the International European Research Project PROPATH of the PROEU-HEALTH cluster. Microbial Ecology in Health and Disease 16:125-130. Δείκτης Απήχησης: 0.780, Αναφορές: 16

2004

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 Jan;40(1):227-32.

2002

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 Medica, 2001:67,880-3.

Petridou Ε, Dalamaga M, Mentis A, Skalkidou A, Moustaki M, Karpathios T, Trichopoulos D, and the Childhood Haematologists-Oncologists Group. Evidence supporting the infectious aetiology of child-hood leukaemia: the role of low herd immunity. Cancer Causes Control Journal, 2001:12,645-52.

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. Nat Prod, 2001:64, 1093-4.

2001

Georgopoulos, S. Ladas, S Karatapanis, AF Mentis, Ch Spiliadi, V. Artikis, SA Raptis. Factors that may affect treatment outcome of triple Helicobacter pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin. Dig Dis Sci, 2000;45:63-67.

2000