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Volume 6
Journal of Infectious Diseases and Therapy
ISSN: 2332-0877
Infection Congress 2018
March 01-02, 2018
March 01-02, 2018 Berlin, Germany
5
th
International Congress on
INFECTIOUS DISEASES
Consequences of
H. pylori
infection and its VacAcytotoxin on mitochondria and mitochondrial DNA:
Impact on gastric pathogenesis
Eliette Touati
Institut Pasteur, France
Statement of the Problem
: Mitochondria alterations and mitochondrial DNA (mtDNA) instabilities are a hallmark of cancer.
Mitochondria represent strategic targets for pathogens also including
Helicobacter pylori.
This bacterium is a major risk factor
for gastric cancer. Up to now, the cytotoxin VacA is the only one
H. pylori
factor known to target and damage mitochondria.
Methodology &Theoretical Orientation
: By in vitro infection of gastric epithelial cells with wild-type and VacA-deficient
H.
pylori
strains, treatment of cells with purified VacA proteins and infection of a mouse model, we show that
H. pylori
deregulates
mitochondria by two novel mechanisms, both rather associated with host cell survival. First, early upon infection VacA induces
transient increase of mitochondrial translocases and a dramatic accumulation of the mitochondrial DNA replication and
maintenance factors POLG and TFAM. These events occur when VacA is not detected intracellularly, therefore do not require
the direct interaction of the cytotoxin with the organelle. They occur independently of the VacA vacuolating activity. In vivo,
these alterations coincide with the evolution of gastric lesions towards severity, concomitantly with the induction of mtDNA
mutations and depletion of mtDNA content. Second, H. pylorus also induces VacA-independent alteration of mitochondrial
replication and import components, suggesting the involvement of additional
H. pylori
activities in mitochondria-mediated
effects.
Conclusions & Significance
: Our findings reveal a novel and early inducer effect of
H. pylori
infection on mitochondrial
translocases and themtDNA replication/transcriptionmachinery components POLG and TFAM. Moreover, we show that VacA
does not account for all consequences of
H. pylori
infection at mitochondria, pointing to the involvement of other bacterial
activities, yet to be determined. These effects of
H. pylori
infection are also relevant in vivo, suggesting that mitochondrial
alterations impact H. pylori-induced gastric inflammation and pathogenicity.
Recent Publications
1. Chatre L, Fernandes J, Michel V, et al (2017)
Helicobacter pylori
targets mitochondrial import and components of
mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent
mechanisms. Scientific Reports 7: 15901.
2. Majlessi L, Fadel Sayes F, Bureau JF, et al (2017) Colonization with
Helicobacter
is concomitant with modified gut
microbiota and drastic failure of the immune control of
Mycobacterium tuberculosis
. Mucosal Immunology 10:1178-
1189.
3. Matak P, Heinis M, Mathieu J, et al (2015) Myeloid HIF-1 is protective in
H. pylori
mediated gastritis. J of Immunology
194:3259-3266.
4. Fernandes J, Michel V, Carmolinga-Ponce M, et al (2014) Circulating mitochondrial DNA level as a potential non-
invasive biomarker to the early detection of gastric cancer. Cancer Epidemiology, Biomarkers and Prevention 23:2430-
2438.
5. Correia M, Casal S, Vinagre J, Seruca R, Figueiredo C, Touati E and Machado J C (2014)
H. pylori
cholesterol uptake
impacts resistance to docosahexaenoic acid. Int. J of Medical Microbiology, 304: 314-320
Biography
Eliette Touati is currently working as a Senior Researcher at the Institut Pasteur in Paris. Her present work is dedicated to the study of the relationships between
H. pylori
infection and gastric cancer, focusing on the regulation of the host DNA damage and repair response. She works on translational projects to characterize
gastric cancer biomarkers with the goal to develop non-invasive tests for the early detection/prevention of patients.
eliette.touati@pasteur.frEliette Touati, J Infect Dis Ther 2018, Volume 6
DOI: 10.4172/2332-0877-C1-038