Nadia Berkova has her expertise in a host-pathogen interaction. Her research interest focuses on the molecular understanding of immunological pathways and analysis of gene expression in the context of immune deregulation of the organism. Actually, she investigates the mechanistic strategies of pathogens to subvert the host defense for their own benefit. Her team identified several staphylococcal cyclomodulins, the family of bacterial effectors that induce eukaryotic cell cycle alterations, and demonstrated the involvement of these bacterial compounds in the alteration of the host immune response. These findings are important for the development of new anti-infective and anti-inflammatory strategies
Statement of the Problem: Bacterial cyclomodulins are a growing family of microbial virulence factors that not only alter host cell cycle progression, but that also interfere with host cell activity, thus favoring the hijacking of host cell protective functions for their own benefit. Staphylococcus aureus (S. aureus), a highly versatile Gram-positive pathogen can cause life-threatening infections. The implications of S. aureus in the alteration of the eukaryotic cell cycle and the biological significance of such an alteration has not been fully investigated. The purpose of the study is to explore the mechanism and to identify staphylococcal compounds that caused host cell cycle arrest and to evaluate the benefit provided by cyclomodulins to bacteria. Methodology & Theoretical Orientation: Flow Cytometry analysis, size exclusion chromatography, mass spectroscopy analysis, Western blotting and immunofluorescence methods were used to identify staphylococcal cyclomodulins and characterize the mechanism. Findings: We demonstrated that S. aureus-induced G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3. Phenol-soluble modulin a (PSMa) peptides were found responsible for this effect. The use of S. aureus mutants confirmed the findings. We showed that the G2 phase was preferential for bacterial proliferation and found that PSMa-induced G2/M transition delay correlated with a decrease in the defensins genes expression. We demonstrated that additionally to secreted staphylococcal cyclomodulins the membrane-anchored lipoprotein-like proteins exert cyclomodulin activity. Conclusion & Significance: Our findings demonstrate that an alteration of the eukaryotic cell cycle enhances an infective efficiency of bacterial pathogens, suggesting that such an alteration may be used by S. aureus for propagation within the host. Moreover, the correlation of PSMa-induced G2/M transition delay with a decrease in the defensins genes expression suggests a reduction of antibacterial functions of infected cells.
Dr Sanjib Bhakta is a world-leading TB-expert and academic head of the ISMB-Mycobacteria Research Laboratory at the Institute of Structural and Molecular Biology (http://www.bbk.ac.uk/biology/our-staff/academic/sanjib-bhakta). His continued research interest in global infectious diseases (funded by Wellcome Trust, Research Council-UK, EU and International Newton Fund) is focussed on developing novel therapeutics as well as repurposing existing drugs to tackle antimicrobial resistance and persistence in TB. He has published around 100 original research articles for a number of internationally acclaimed journals viz. J. Exp. Med., J. Biol. Chem., Tuberculosis, Biochemical Journal, Journal of Antimicrobial Chemotherapy, FEBS J, Molecular Microbiology, British Medical Journal, British Medical Bulletin, PLOS and Journal of Medicinal Chemistry. As a UK-STEM ambassador and BSAC-Antibiotic Action Champion, Dr Bhakta has volunteered on the Wellcome Trust/Research Council-UK funded programme “Researchers in Residence” at local schools in London and has contributed to British Museum science programme “News & Views”.
Repurposing common non-steroidal anti-inflammatory drugs (NSAIDs) could potentially reverse intrinsic antimicrobial resistance in TB
Gwénaël Jan research activity focuses on the “2-in-1” properties of selected strains of dairy bacteria, both as starters for fermented dairy products, and as probiotic beneficial microbes. Following a PhD in Rennes University and Post-doc in Aberdeen Institute of Medical Sciences, he joined INRA in 1998 to study probiotic abilities of dairy propionibacteria. In close collaboration with INSERM, Pasteur Institute, Rennes University Hospital, as well as with dairy industry stakeholders, he develops a research activity spanning from food technology and molecular microbiology to preclinical and clinical investigations
Why buy probiotics while they are already in your fridge? The 2-in-1 effect of dairy bacteria as both immune modulators and cheese starters.
Ebtesam Al-Ali obtained her BSC in 1993 from Kuwait University Worked for Kuwait University as Research Assistant, then joined KISR on October 5, 1993 and led six projects; she has published more than 25 papers in reputed journals and international conferences. Her field of experience, in plant virus detection, primer design, cloning and sequencing, ELISA, DNA Extraction, PCR Amplification, RCA Rolling Circle Amplification, TYLCV detection on tomatoes, also trained twice in the University of Wisconsin Madison under the supervision of Prof. Amy Charkowski. As well as University of Washington state under supervision of Pro.Hanu Pappu.
Phylogeonography and Molecular Characterization of Tomato Yellow Leaf Curl Virus in Kuwait