Medical Microbiology

Research in the LMM is centered on mechanisms by which mainly bacterial, but also viral pathogens can manifest their pathogenic role. The model organism studied is the human gastric pathogen Helicobacter pylori, which has been recognized as the etiologic factor for the development of chronic gastritis and peptic ulcer and has been classified as the primary risk factor for the development of gastric adenocarcinoma (class 1 carcinogen, by WHO). LMM functions as a National Reference Laboratory for Helicobacter infections, since present activities fully extend to diagnosis of the infection, laboratory surveillance of antimicrobial susceptibility of clinical isolates, full virulence factor characterization in H. pylori isolates, phylogenetic analysis of clinical isolates, based on specific gene or whole genome sequencing and preservation of a complete Biobank of clinical strains. LMM staff has participated in the team of microbiology experts set by the Hellenic Society of Gastroenterology, for the preparation of the consensus statement on the diagnosis, clinical management and treatment of H. pylori infection, in Greece (Georgopoulos et al., Hellenic consensus on Helicobacter pylori infection. Ann Gastroenterol. 2020)

Main scientific directions include:

Study into the mechanisms of Helicobacter pylori pathogenesis

Tissue remodeling of the extracellular matrix, through the induction of matrix metalloproteinases (MMPs) in the H. pylori infection. Identification and mapping of basic signaling pathways that lead to the activation of the particular MMP-specific or MMP-related determinants and promote Epithelial- to-Mesenchymal-Transition (EMT) (I. Karayiannis PhD project; Karayiannis in preparation 2022).

Impact of Helicobacter pylori infection in the deregulation of DNA damage response mechanisms (E. Kontizas PhD project, Kontizas et al., Microorganisms 2020; Kontizas et al., Microb Health Dis 2021) and collaboration with Dr. Eliette Touati, Institut Pasteur, Unité de Pathogenèse de Helicobacter), collaborative PTR-332 program

CagA-dependent microRNA-mediated post-transcriptional regulation of gastric epithelial cells in Helicobacter pylori infection (E. Sotiropoulou PhD project; Sotiropoulou et al., in preparation 2022)

Laboratory surveillance of H. pylori antibiotic susceptibility to common antibiotics used in the patient eradication schemes in collaboration with Alexandra, Evangelismos, Laikon, Aghia Sophia Children Hospital, Mitera Hospital, Athens Medical, Paleo Faliron Hospital Gastroenterology Clinics in Athens (in collaboration with Dr. B. Martinez-Gonzalez) and participation in prospective clinical studies for the evaluation of eradication efficiency (Georgopoulos et al. Ann Gastroenterol 2018; Georgopoulos et al. Eur J Intern Med 2016; Georgopoulos et al. Helicobacter 2013)

Phylogenetic analysis of H. pylori clinical isolates and mapping of human migrations through history. An international collaborative effort to analyze genetic variation in H. pylori genome sequences and thereby determine the phylogeographic pattern of human migrations. Collaboration with Dr. Daniel Falush, Institut Pasteur Shanghai (Thorpe et al. bioRxiv, doi: https://doi.org/10.1101/2021.06.05.447065)

Whole genome sequencing analysis of H. pylori clinical isolates from gastrointestinal tumors and identification of molecular features that contribute to pathology by comparing the profile of benign infection to corresponding spectra of isolates from individuals with gastric cancer and premalignant lesions such as, atrophic gastritis and intestinal metaplasia. Collaboration with Dr. M. C. Camargo and Dr. C. Rabkin MD, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, USA. (In collaboration with Dr. Martinez-Gonzalez)

Assessment of putative anti-bacterial and anti-inflammatory activity of new drugs, natural products and probiotics utilizing in vitro and in vivo infection systems. Collaboration with Prof. E. Tsakalidou of the Agricultural University of Athens on the identification and isolation of probiotic lactobacilli from traditional food sources (Saliba et al. International Dairy Journal 2021; Mangia et al. Fermentation 2019) and study of the effect of Chios mastic gum effect on the oral microbiome (Collaboration with Prof. A Hatzigeorgiou and Dr. Martinez-Gonzalez at HPI– The Schinos project)

Laboratory surveillance and phylogenetic analysis of viruses and parasites in collaboration with the Public Health laboratories of HPI. Phylogenetic analysis of respiratory viruses (Collaboration with Dr. A. Mentis until 2020 and Dr. U Georgopoulou since 2021) and Hepatitis C virus (in collaboration with Dr.Martinez-Gonzalez)

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, GES-1)
• pylori in vivo animal models (Sydney Strain 1, HPARE, PMSS1 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.

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 has developed novel methods for the metagenomic determination of the composition of microbial communities, based on next generation sequencing technologies. 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. Consequently, LMM has participated through ERINHA2 H2020-INFRADEV-1-2015-2 in the preparative phase of the ERINHA framework and the research portfolio. LMM staff has also participated actively during the SARS-CoV2 pandemic supporting the Diagnostic Services in the identification of active cases.

CURRENT RESEARCH PROGRAMS

PAST RESEARCH PROGRAMS

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