Day 1 :
University of London and UCL, UK
Keynote: Repurposing common Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) could potentially reverse intrinsic antibiotic resistance in the TB-causing superbug
Time : 08:45-09:15
Sanjib Bhakta is a full Professor of Molecular Microbiology and Biochemistry, Strategic Dean (Internationalisation and Partnership) and Programme Director of MRes Global Infectious Diseases at the Institute of Structural and Molecular Biology, Birkbeck, University of London and UCL His continued research interest in infectious bacterial diseases (funded by Wellcome Trust, Medical Research Council, UK and EU) is focused on developing novel therapeutics as well as repurposing existing drugs to tackle antibiotic resistance and persistence in tuberculosis (TB), a global health and economic emergency. To date, he has published more than 100 original research articles for a number of internationally acclaimed journals including J. Exp. Med., JBC, Tuberculosis, Biochem. J., JAC, FEBS J, Mol Micro, British Medical Journal, PLOS, J. Med Chem and Nat Sci Report.
The rise of antimicrobial resistance is leading to ever-more untreatable illness. Intracellularly surviving bacterial pathogens have endogenous machinery to evade host defenses as well as antibiotic treatment. Drug efflux and formation of biofilms are the two key fundamental mechanisms of intrinsic resistance which render many antibiotics ineffective against them. Mycobacterium tuberculosis has unique multi-drug transporter protein complexes that allow the pathogen to take up nutrients for survival, while allowing it to extrude deleterious ones so as the signaling molecules for quorum-sensing leading to biofilm formation. Our work has shown that the non-steroidal anti-inflammatory drugs (nsaids) have anti-bacterial action against Mycobacterium tuberculosis. The most potent NSAID so far, at sub-inhibitory concentrations, inhibited whole-cell efflux pumps activity at par with/better than potent efflux pump inhibitors such as verapamil and chlorpromazine. In addition, the NSAID inhibited mycobacterial biofilm formation significantly. Analysis of the extracellular polymeric substances of treated biofilm showed macromolecular alterations compared to the untreated controls. Furthermore, transcriptomic analysis revealed modulation of key metabolic pathways in NSAID-treated M. Tuberculosis revealing novel endogenous targets of the drug. The over-the-counter immunomodulatory drug’s new antibiotic action has paved an alternative route for tackling antimicrobial resistance in tuberculosis (TB).
University of London, UK
Keynote: Evaluation of antimicrobial activity of designed peptides against a Novel Class A β-lactamase in Klebsiella pneumoniae
Time : 09:15-09:45
Karina Caetano Souza has completed her BSc Biomedicine and holds a Chemistry Technician Degree. Currently pursuing MRes Global Infectious Diseases research-intense programme. Ms Souza is one of the 16 European students selected for a prestigious DUO-India 2020 academic exchange programme. This academic exchange programme created to facilitate educational exchanges between Asia and Europe and encourage academic research collaborations.
Klebsiella pneumoniae is a Gram-negative bacterium that is one of the WHO’S priority ESKAPE pathogens which are responsible for a significant increase in mortality worldwide. It has also caused a massive economic burden due to presenting multidrug resistance in the causal pathogen at an alarming rate. The aim of this project is to reverse β -lactam drug resistance in Klebsiella pneumoniae by binding designed peptides (designed in silico, produced and purified) to the active site pocket of a novel Class A β – lactamase. Antibiotic sensitivity assessment of the cells harbouring the β – lactamase in presence and absence of the peptides have shown some promising results. Alongside this, expression and purification of the novel β – lactamase is being approached for further structure-activity relationship studies.
National University of Sciences and Technology “NUST”, Oman
Keynote: How far is the effect of Subminimal Inhibitory Concentration (Sub MIC) on virulence factors expressed by bacteria?
Time : 09:45-10:15
Nida’a Mohammed Ali Wadi is a Register Pharmacist for more than 30 years. She is a Sr. lecturer at Oman Medical College (currently named NUST, National University of Science and Technology). She has practiced as a Lecturer in Medical College and Sr. lecturer Pharmacy College for several years. She has many contributions as Speaker, Poster Presenter as well as published some articles. She teaches in the graduate pharmacy program different pharmacy subjects and she is Chairperson of training program for national and international training Coordinator with West Virginia Pharmacy College, USA & JSS India. Her interest of research is on antibiotic resistance (Beta Lactamases) and formulation and evaluation of local delivery system.
Antibiotic medications are widely used in the treatment and prevention of various infections. An increase in the rate and extent of antibacterial action can be ranged over a wide of antimicrobial concentration but should be within minimum inhibitory concentration where this concentration represents the Minimum effective of antibacterial agent (MIC). Sub inhibitory antimicrobial concentration (Sub MIC) may produce antibacterial effect. The major virulence factors associated with infections are the ability to adhere to tissue and initiates interaction of bacterial cell with tissue. It is potential in the pathogenesis of certain infectious disease. Agents interfering with the process of bacterial adhesion may have beneficial prophylactic or therapeutic effects. Many studies indicate that certain antibiotics affect bacterial adhesion at low concentrations. Sub inhibitory concentrations (Sub MIC) of some antibiotics may have an effect on bacterial structure and influence the adhesion of bacterial adhesion to epithelial cells. It has been observed that the pili play an important role in the attachment and an important prerequisite factor for the pathogenesis of the bacteria. Various antibiotics in Sub MIC concentrations markedly impair adhesion of Streptococcus pyogenes and Escherichia coli to human cells like loss of lipoteichoic acid that binds the organism to host cells. In this study certain characters of the isolated pathogen in vitro and the presence and absence of pili on the surface of the organism were studied. We utilized an in vitro assay system to study the effect of Sub MIC of various antibiotics on Escherichia coli. The results demonstrate that some antibiotics change the adhesiveness of Escherichia coli strains. Subminimum inhibitory concentration of various antibiotics showed the ability to reduce the colonization. Investigating the effects of Sub MIC antibiotics bacterial adhesion to epithelial cells may lead to the development of future antibiotic treatment modalities and may suggest a new parameter for the use and the study of antibacterial agents.
National University of Pharmacy, Ukraine
Keynote: Consumption of antibacterials for systemic use (ATC group J01) in Ukraine in 2013-2018 compared to the United Kingdom
Time : 10:30-11:00
Larysa Iakovlieva is Doctor of Pharmaceutical Sciences, Professor. She has extensive experience in pharmacological and pharmacoeconomic research. In 2004, she opened the first pharmacoeconomic department in Ukraine. In 2012-2015, collaborated with WHO on antibiotic resistance. Larysa V. Iakovlieva is a member of the Expert Committee on the Establishment of the National List of Essential Medicines of the Ministry of Health of Ukraine.
Statement of the Problem: Researchers have reported that antibiotic resistance (ABR) is one of the biggest threats to global health, food security, and sustainable development today. An analysis of the relationship between the levels of antimicrobial drug consumption and the development of antibiotic resistance is one of the tools to contain the resistance.
The purpose of this study is to analyze the consumption in the community of antibacterials for systemic use (AB) (ATC group J01) in Ukraine (UA) in comparison with the United Kingdom (UK).
Methodology & Theoretical Orientation. The DDDs per 1000 inhabitants per day (DID) were used to calculate the consumption of antibacterial agents using the ATC / DDD methodology recommended by the WHO. The calculations were carried out according to the analytical system of the pharmaceutical market research “Pharmstandard” of “Morion” company. Consumption data for the UK were obtained from the Annual epidemiological report for 2018 (European Centre for Disease Prevention and Control).
Findings: Over the last 6 years, AB consumption in the UK has decreased from 18.3 DID in 2013 to 16.3 DID in 2018, despite a slight increase in 2014 (18.5 DID). Consumption indicators in UA decreased from 11.6 DID in 2013 to 10.1 DID in 2015 and increased from 11.1 DID in 2016 to 12.5 DID in 2018. The largest difference in AB consumption between the two countries was recorded in 2015 (1.8 times). In 2018, this difference was 1.3 times.
Conclusion & Significance: The ability to buy antibiotics without prescription in Ukraine does not play a significant role at the level of consumption.This may indicate that low levels of financial support in Ukraine are forcing the population not to use antibiotics for treatment. Also a high fear of the side effects of antimicrobials contributes to their low use.
Indian Institute of Technology Kharagpur, India
Keynote: Characterisation of peptides designed against the omega loop of class A β-lactamases to reverse antimicrobial resistance in bacteria
Time : 11:00-11:30
Sarmistha Biswal is an ASEM-DUO (UK-India) Exchange Fellow between Indian Institute of Technology (IIT), Kharagpur, India and the Institute of Structural and Molecular Biology, Birkbeck, University of London. She is a young woman investigator whose current research interest is in tackling antibiotic resistance in infectious bacterial diseases. She has published peer-reviewed research articles and presented her research in international meetings.
Mycobacterial infections result in huge damage to public health and economy each year because of the alarming emergence of extensively drug-resistant strains of Mycobacterium tuberculosis (WHO, 2019). Mycobacteria have long known to be intrinsically resistant to β-lactam antibiotics. Β-lactamases are enzymes those protect bacterial cells by hydrolyzing β-lactam ring of antibiotics making them ineffective. Class-A β-lactamases have a conserved structural domain called omega loop (RLDRWETELNEAIPGDARD) participating in catalytic activity being a part of the drug-binding pocket of the enzyme. In this work we have attempted to design and characterize some peptides against the omega-loop of class A β-lactamases to reverse antimicrobial resistance in bacteria. Primarily, about 100 peptides were designed against the conserved sequence of omega-loop of class A β-lactamases. The peptides sequences were subjected to different bioinformatics tool and finally, 10 peptides were synthesized by Fmoc Solid-Phase Synthesis Peptide (SPPS) strategy (J.M. Palomo, 2014). Whole-cell phenotypic evaluations were done to ascertain the hydrolytic potential of pbad-blatem1 (class A β-lactamases) against different β-lactam antibiotics in presence of all the synthesized peptides in different bacteria (E. Coli CS109, Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv) and we observed a significant decreased level of hydrolytic activity of blatem1 in the presence of peptides. Thus, the study may explore the role of peptides in masking of omega-loop facilitating β-lactams to kill the bacteria.