Immunology, Transplantation and Infectious diseases

Emerging bacterial pathogens

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Group leader

Daniela Maria Cirillo

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Infections caused by bacteria are difficult to treat and are major killers worldwide. It is estimated that by 2050 infections by multidrug resistant pathogens will cause more than10.000 deaths worldwide. While drug resistant bacterial pathogens are emerging and spreading in community and nosocomial environment increasing health care costs, in low to middle income countries M.tuberculosis (MTB) claims annually more lives than any other pathogens. The deadliest form of tuberculosis is caused by MTB resistant to the drugs used worldwide for treatment.

The mission of EBPU is to increase the capacity worldwide to diagnose and treat properly tuberculosis and other drug resistant bacterial pathogens to stop the epidemic. We focus on different areas: pathogenesis of mycobacteria infections (tuberculosis and disease caused by non-tubercular mycobacteria), mechanisms and evolution of drug resistance in bacterial pathogens both mycobacteria and drug resistant pathogens health-care associated, phylogenesis and transmission studies. We perform research on new diagnostic strategies for different DR pathogens to optimize pathogen’s detection and drug resistance profile from clinical samples.

Research activity

Research lines are supported by competitive grants or international agencies dedicated funds.

  • host-pathogen interaction: We study the “host pathogen” interaction on “in vivo” and “ex vivo” models developed in the past years (Pellin,Miotto et al 2012, Furci et al 2013; Baldan et al, 2014; Riva et al,2020; Nicola et al 2023). The “ex-vivo model” has been used to discover MTB sRNAs role in pathogenesis and drug resistance development (Pellin,Miotto et al 2012; Chiacchiaretta et al submitted, 2024). Pathogenesis of M.abscessuss lung disease induced by strains with different virulence is approached with different new technologies to understand the cross talk between the host and the pathogen (Bar-Oz et al 2023; Lorè et al 2022).  

  • New diagnostics: for the past 20 years we have conducted research on new diagnostic strategies for diagnosis of tuberculosis and other mycobacterial diseases (Piana et al, 2006;Tortoli et al, 2012; Miotto et al 2013; Tagliani 2015; Barcellini et al 2016; Rancoita et al 2018; Nikolayevskyv et al,2019; Dorman et al 2018; Cabibbe et al 2020). With the support of several projects we focused on genomic as a tool for characterization of the mutations responsible for drug resistance to the different agents (Miotto et al 2017). We have optimized and evaluated many diagnostics providing to WHO data to inform policies. We now work on both pathogens and host molecular signatures that could be used as markers of progression or cure. Use of omics to study phylogenesis and correlation between phenotype and genotype to interpret drug resistance: we have analyzed more than 15000 genomes from MTB, NTMs and MDRO of nosocomial origin. Our bioinformatics are engaged in improving pipelines to improve identification of virulence determinants, transmission of drug resistance mechanisms by using long and short reads sequencing strategies (Khol et al 2018; Di Marco 2023). Alternative to “canonical samples” to perform diagnosis of pathogens are emerging, we are defining the performance of innovative diagnostic strategies based on exhalate as non-invasive tools to perform diagnosis and surveillance of airborne transmissible pathogens.

  • Phylogenesis, bacterial genome analysis and cluster studies we use curated genomes to refine taxonomy, study phylogenesis, emergence of drug resistance and molecular epidemiology of DR pathogens(Tortoli et al 2016; Tortoli, 2017; Tagliani 2021 Yenew Ghodousi et al 2024)

  • Clinical trials for new antitubercular drugs and therapeutic strategies against DR pathogens. Two main projects are ongoing. Unite4TB is the largest phase 2B, C trial ever conducted for new antitubercular drugs. Our task is to unravel the mechanisms of drug resistance to those drugs, define tools for detection and understand possible cross-reaction in addition to provide microbiology monitoring to the trial’s sites. KP-protect supports the development of monoclonal antibodies specifically directed against DR Klebsiella pneumoniae to be used in patients with severe infection or to prevent colonization in fragile population.

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