Friday, 27 April 2018

Molecular basis of major antibiotic resistance transfer mechanism unraveled


Bacteria have developed resistance to most of the drug compounds we use today. Examples of multi-drug resistant bacteria include organisms that are part of our normal microbiome and thus hard to eradicate, such as MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), and ESBL (extended spectrum beta-lactamase) producing Enterobacteriaceae.

One of the major drivers of resistance spreading between bacteria are transposons -- also called jumping DNA: genetic elements that can switch locations in the genome autonomously. When transferred between bacteria, transposons can carry antibiotic resistance genes within them.

The research of the Barabas group at EMBL focuses on transposons and their molecular structure. The team now provides the first crystal structure of a protein-DNA machine that inserts the transposons, including the resistance they carry, in recipient bacteria.

The research team discovered that the workhorse of the transposon insertion machine, the transposase protein, has an unusual shape (SEE IMAGE). This enables it to bind to the DNA in an inactive state, which prevents cleavage and thus 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 cargo at many places in an extremely diverse range of bacteria.

For further information, see:

Anna Rubio-Cosials, Eike C. Schulz, Lotte Lambertsen, Georgy Smyshlyaev, Carlos Rojas-Cordova, Kristoffer Forslund, Ezgi Karaca, Aleksandra Bebel, Peer Bork, Orsolya Barabas. Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic ResistanceCell, 2018; DOI: 10.1016/j.cell.2018.02.032

Posted by Dr. Tim Sandle

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