Bacteriology axis : Research group Ahalieyah Anantharajah and Michel Delmée (CNR Clostridioides difficile)


Michel Delmée and his group have focused their research on the epidemiology of Clostridioides difficile infections in hospitals. This Gram-positive anerobic spore-forming bacterium is the main cause of diarrhea occurring after antibiotic therapy, with a clinical spectrum ranging from trivial diarrhea to pseudomembranous colitis, which is sometimes fatal. It is estimated to be responsible for 10-25% of antibiotic-associated diarrhea and almost all cases of pseudomembranous colitis.
The development and evaluation of new diagnostic approaches on the one hand, and the development of typing techniques applied in epidemiological surveillance programs on the other hand, have been the two major lines of research since the discovery of the pathogenic role of this bacterium in the late seventies.
Since 2011, the laboratory has been designated National Reference Center. As such, it organizes with Sciensano a national surveillance program in which all Belgian hospitals can participate. The serogrouping technique for C. difficile was one of the first to be described in 1985 and has been used in many international epidemiological programs. Over the last 15 years, molecular biology techniques have supplanted other approaches. Currently, clinical isolates are characterized by the PCR-ribotyping technique. This technique is considered in Europe as the reference method. A constant work of nomenclature harmonization is carried out in collaboration with different European teams in order to allow the comparison of strains on an international scale. At the CNR, more than six hundred different profiles have already been identified.
At the same time, a characterization of the main virulence factors produced by C. difficile is being carried out. Indeed, since the beginning of the year 2000, infections have taken another dimension, especially with the appearance of new and more virulent strains. These strains of type 027/NAP1/BI have been associated with severe epidemics with high mortality rates. Indeed, they produce much higher quantities of toxins A and B than the usual strains of C. difficile and secrete the binary toxin. The hyperproduction of toxins A and B is thought to be related to deletions in the tcdC regulatory gene, resulting in a frameshift and a truncated TcdC protein. In addition, epidemic NAP1/027 strains are resistant to many antibiotics, including fluoroquinolones, which may have given them a selective advantage.
Continuous surveillance is necessary to know the epidemiology of Clostridioides difficile isolates circulating in Belgium and to monitor the emergence of hypervirulent and/or resistant strains. The NCRC also participates in several European programs coordinated for the ECDC.
In addition to surveillance, the CNR's mission is to assist clinical laboratories in the diagnosis of toxigenic C. difficile, in the implementation of new tools and in the investigation of outbreaks or relapses of C. difficile infection in the same patient. Isolates can be analyzed by MLVA (MultiLocus Variable number tandem repeat Analysis) which allows to differentiate strains within the same ribotype.
Currently, the CNR is implementing genomic approaches such as WGS (Whole genome Sequencing), in order to better understand the virulence of certain clinical isolates and to investigate the clonal relationships of clustered cases.