Frequent and inappropriate use of antibiotics poses a serious health risk. Multidrug-resistant bacteria, often referred to simply as “superbacteria” in the media, are resistant to several antibiotics, have become widespread and are responsible for many deaths worldwide. Hospitals and health care facilities are the focal points for the development of bacterial infections, where antibiotics are widely used and pathogens can spread easily among patients. In the current situation, there is an urgent need to develop new, effective antibiotics; therefore, the research group of the Synthetic and Systems Biology Unit within the Institute of Biophysics of the ELKH Szeged Biological Research Center (BRC) started to develop antibiotic molecules that may be effective against superbacteria.
According to a survey conducted by the European Center for Disease Prevention and Control, multidrug-resistant pathogens caused pneumonia and bloodstream or urinary tract infections in 8.3% of patients admitted to intensive care units in 2017 in Europe. In addition to the additional costs of prolonged treatment, these infections very often result in the deaths of patients – according to WHO data from 2019, this accounts for 700,000 mortalities a year. It is estimated that this number could increase in the future to such an extent that resistant infections could claim more deaths than cancer by 2050. Obvoiusly, the problem of resistance also affects Hungary. The most common infections in Hungarian hospitals are caused by Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and MRSA, which is a well-known example of resistant superbacteria.
New antibiotics are needed
In the current severe crisis, in addition to a change of approach globally, there is an urgent need to develop new, effective antibiotics, but this process has slowed down considerably in recent years. Since bacteria can become resistant extremely quickly, new antibiotics prove ineffective shortly after they are placed on the market, or often even during the testing process. Because the huge amount of time and money invested in the development process does not pay off, pharmaceutical companies are becoming less and less interested in antibiotic development, and some companies, e.g. Novartis and Sanofi, have completely halted research in this area. If we were more careful at the very beginning of the development process, we would be more likely to find agents that would remain effective for a longer period of time. This requires a novel and rational approach to designing molecules. By modifying their design and structure, specific molecules can be created against which bacteria find it more difficult to develop resistance.
One dangerous pathogen: MRSA
The goal of Csaba Pál’s research group is to develop antibiotic molecules that are effective against MRSA infection caused by the methicillin-resistant Staphylococcus aureus bacterium, or MRSA for short. MRSA is one of the most dangerous pathogens in Europe, including Hungary. There are countries where it causes more infections and often fatal conditions than any other infectious disease combined. Some estimates put the associated global health care costs at USD 5 billion a year. Antibiotics currently on the market and under development do not offer a satisfactory solution because MRSA adapts extremely quickly to new antibiotics.
In close professional collaboration with the University of Ljubljana, the research team designed two qualitatively new antibiotic candidates, called ULD1 and ULD2. The special property of these molecules is that they have several targets within the bacterial cell, so the development of resistance is minimal. Preliminary experiments in mice show that ULD1 and ULD2 are particularly effective against MRSA skin infections, and at the same time, they have no detrimental effect on human cells. Csaba Pál et al. demonstrated that antibiotics on the market or under development are ineffective against many genetic variants of MRSA. In sharp contrast, ULD1 and ULD2 effectively eradicated all MRDA variants tested under laboratory conditions. Therefore, the international patenting process for this family of molecules is already in progress.
With the support of the National Biotechnology Laboratory, which will be launched in the near future, it has become possible to develop new, even more effective antibiotic candidates and to further test promising molecules. The ultimate goal is to make the molecules marketable to internationally significant drug development companies. The research appeared of the pages of the prestigious Plos Biology publication:
He received his doctoral degree at Eötvös Loránd University in 2002 and then spent several years abroad on a scholarship, studying in Oxford and Heidelberg. Since 2008, he has been a researcher at the Szeged Biological Research Centre of the Eötvös Loránd Research Network, a senior researcher at the Institute of Biochemistry, and one of the heads of the Synthetic and Systems Biology Unit. He specializes in antibiotic resistance and genome engineering. In the course of his career, he was awarded the European Research Council’s Starting (2008-2013), Consolidator (2015-2020) and Proof of Concept (2019–) grants, earning his research team EUR 3.5 million in direct funding. He has published more than 50 scientific papers in prestigious journals such as Nature, Nature Microbiology, Nature Genetics, Science and PNAS. His research work has been recognized by several prizes. In 2009, he won the Ignaz L. Lieben Prize of the Austrian Academy of Sciences, he was awarded the Szent-Györgyi Talent Prize in 2014, and the János Bolyai Creative Prize in 2015. He has been a member of Academia Europaea since 2016, the European Organization for Molecular Biology (EMBO) since 2017, and the Federation of European Microbiological Societies since 2018. He is also a member of the editorial boards of Molecular Biology and Evolution, Plos Biology and Biology Direct.
Further details: http://group.szbk.u-szeged.hu/sysbiol/