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:
Posted by Dr. Tim Sandle
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Pharmaceutical Microbiology