Infection by S. aureus is a serious threat in hospitals worldwide. Now,
scientists have identified a key component of the machinery that allows
Staphylococcus aureus to transfer genes that confer antibiotic resistance.
Halting the spread of resistant bacterial strains is one of the strategies
available to tackle hospital infections.
Antibiotic resistance of the bacterium
Staphylococcus aureus is responsible
for 11,300 deaths a year in the United States alone -- a figure that
corresponds to half of all deaths caused by gram-positive resistant bacteria in
that country. Such high mortality is related to the speed at which the
bacterium acquires resistance to antibiotics. A study performed at the
Institute for Research in Biomedicine (IRB Barcelona) and involving the
collaboration of the Centro de Investigaciones Biológicas (CIB-CSIC) in Madrid
has identified the key component of the machinery that S. aureus uses to
acquire and transfer genes that confer resistance to antibiotics.
Horizontal gene transfer involves
machinery in which the relaxase, an enzymatic protein, is a key component.
Thanks to the 3D resolution of the structure of the complex formed by the
relaxase with a fragment of the plasmid DNA, the researchers have identified
that an amino acid histidine is a pivotal element in the DNA processing and
thus in the transfer and the spread of resistance.
"What we have discovered is that
the relaxase of diverse strains of S. aureus differs because it uses an amino
acid that is not used by any other relaxase that we know of," explains the
first author of the study, Radoslaw Pluta, former "la Caixa" PhD
student at IRB Barcelona, and currently a postdoctoral researcher at the
International Institute of Molecular and Cell Biology in Warsaw, Poland.
Histidine is the catalytic residue
that allows the relaxase to cut DNA, bind to it, and stretch one of the two
strands and take it into the receptor bacterium, where the strand replicates to
form a double strand of the plasmid again. This new plasmid now holds the
resistance genes and the machinery to transfer them to another bacterium. The
scientists indicate that this catalytic histidine is present in the relaxases
of 85% of the strains of Staphylococcus aureus.
To test whether histidine is decisive
in horizontal gene transfer,, researchers in Manuel Espinosa's group at the
CIB-CSIC, who participated in the study, replaced it by a different amino acid
and confirmed that it prevents transfer in culture dishes.
The mutation of histidine does not
kill that bacterium but rather prevents gene transfer. How could this mechanism
be exploited to fight infections? This requires further study.
See:
Posted by Dr. Tim Sandle