Monday, March 19, 2018

The War Against Antibiotic Resistant Bacteria

The War Against Antibiotic-Resistant  Bacteria

Antibiotic medications are used to kill bacteria, which can cause illness and disease. They have made a major contribution to human health. Many diseases that once killed people can now be treated effectively with antibiotics. However, some bacteria have become resistant to commonly used antibiotics. Antibiotic-resistant bacteria are bacteria that cannot be killed by antibiotics and are able to survive and multiply in the presence of an antibiotic. This issue has become one of the current threats to global health. Some bacteria that have developed resistance to antibiotics are MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), and ESBL (extended spectrum beta-lactamase) producing Enterobacteriaceae.

One of the key factors that aids resistance spreading between bacteria is transposons. Transposons have the ability to switch locations in the genome autonomously. When transferred between bacteria transposons can carry antibiotic resistance genes within them. Due to this threat, EMBL researchers are in the process of stopping this crisis. Throughout their study, the research team has proposed a molecular structure of transposons that can provide an explanation to the protein-DNA mechanism that inserts the transposons, including the resistance they carry, in recipient bacteria. This mechanism is possible because of the unusual shape of the transposase protein.  This lets it to bind to the DNA in an inactive state, which prevents cleavage and destruction of the transposon until it can paste the antibiotic resistance gene in the new host genome. The protein's special shape also forces the transposon DNA to unwind and open up allowing it to insert its antibiotic resistance lineage at many places in an extremely diverse range of bacteria.

Based on the proposed structure and understanding of the mechanism the EMBL researchers have developed molecules that would block the transposons movement. In theory, these molecules would be able to prevent the development of antibiotic-resistant bacteria. The EMBL researchers proposed two methods, one stops the transposase protein from going to its activated conformation by blocking its architecture with a newly designed peptide, a short chain of amino acids. The second method is a DNA-mimic that binds to the open site within the transposon, thus blocking the DNA strand replacement that is needed for resistance transfer. Of course, these two methods are only potential strategies. Therefore, there is still much more work to be done in the lab before these molecules are classified as being safe to the public.

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