GENetic susceptibility and BIOmarkers in Listeriosis – MONALISA-GENBIO

Listeriosis is a rare and severe infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as a blood infection (septicemia), central nervous system (CNS) infection or maternal-fetal (MF) infection. Diagnosis relies on the culture of biological samples (blood, cerebrospinal fluid, placenta), whose time to results is at least of 2 days, delaying the initiation of appropriate management. Overall mortality is very high, above of 30%, and death most frequently occurs in patients under antimicrobial therapy. Fetal loss occurs in around 20% of maternal cases. The management of infection has not changed over the last 20 years, and outcome has not improved either. A better knowledge on the factors involved in listeriosis occurrence and a better clinical and biological characterization with most advanced techniques will likely improve outcome. A number of acquired risk factors for listeriosis have been identified, such as pregnancy, age, cirrhosis, renal insufficiency, diabetes, cancer, HIV infection, transplantation and corticosteroids. However listeriosis has also been diagnosed in a limited number of young patients lacking such risk factors (5% of the MONALISA cohort). Given its high occurrence in food, the exposure to Lm is universal, and the prevalence of these risk factors in the general population is relatively high. In contrast, listeriosis is rare, including among patients with known risk factors: 350 cases reported annually in France which count 10 millions older people and above 1 million diabetic. This suggests that so far unknown risk factors, including genetic factors, contribute to the susceptibility to listeriosis. Such factors have not been studied so far, in the absence of prospective collection of patients’ samples.
In this context, we launched in 2009 the Multicentric Observational National Analysis of Listeriosis and Listeria (MONALISA) that now compiles over 900 cases, including a large set of clinical data, and biological samples including DNA. MONALISA provides a unique opportunity to study this major aspect of listeriosis, and to identify new biomarkers of infection that would provide a biological signature for infection, and new diagnostic tools, along with a better characterization of listeriosis severity and outcome.
The MONALISA-GENBIO project has two main objectives: (i) to identify genetic factors associated with the occurrence of listeriosis either alone or in combination to other identified risk factors, and (ii) to identify biomarkers associated with listeriosis and those related to poor outcome (prognosis score).
Genetic analyses will be performed on DNA samples of the whole cohort, by genotyping and exome sequencing. Patients’ sera will also be analyzed by two complementary biochemical approaches (multianalyte profiling and metabolomic approach). Their combination will provide better and faster diagnostic and prognostic tools to manage listeriosis.
This collaborative translational project is based on a unique cohort and put together teams with high expertise in their respective field. It will unravel new risk factors for listeriosis and bring up innovative new diagnostic and prognostic tools that will directly improve the management of infected patients at the diagnostic, therapeutic and prevention levels. It may also lead to the identification of at-risk individuals for whom preventive measures may decrease listeriosis incidence.