A combination of drugs can treat antibiotic-resistant bacteria
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Combining antibiotics with drugs that prevent bacteria from making fatty acids may help combat antibiotic resistance.Drug combinations are more effective in treating bacterial pneumonia in mice than antibiotics alone. was.
Bacteria have evolved resistance to antibiotics since they were developed about a century ago. Currently, only a small portion of these drugs can treat specific pathogens, and even these drugs are losing their potency.
Eric Brown and his colleagues at McMaster University in Canada tested the drug combination on two different strains of five bacteria. One strain was resistant to colistin, an antibiotic of last resort that binds to fatty acids in cell membranes to enter and kill bacteria.
In the presence of the drug, colistin-resistant bacteria produce more of a vitamin called biotin. So the researchers applied both colistin and a compound that inhibits biotin production to bacteria.
After 18 hours, they measured treatment efficacy by analyzing how well the drug pair prevented bacterial growth compared to either drug alone. Fractional Inhibitory Concentration (FIC) ) index, this metric ranges from 0 to 1, with lower numbers indicating greater effectiveness.
FIC index values were less than 0.3 for all 5 colistin-resistant strains and greater than 0.5 for all non-resistant strains. This indicates that blocking biotin production increases susceptibility to antibiotics, but only in drug-resistant bacteria.
“One of the reasons biotin is essential for bacteria is that it functions as a cofactor for fatty acid synthesis,” says Brown.
Genetic analysis revealed that colistin-resistant bacteria have alterations in genes related to fatty acid production. These changes prevent colistin from attaching to cell membranes. Therefore, impairing fatty acid production should increase the susceptibility of antibiotic-resistant bacteria to colistin.
To test this, researchers infected 18 mice with colistin-resistant bacteria. Klebsiella pneumoniae, a bacterium that causes pneumonia. An equal number of mice were given colistin, a drug that inhibits fatty acid synthesis, or both. A blood sample taken seven hours later showed that mice given both drugs had more than 99.9% fewer bacteria than those in the other groups, indicating that the drug combination overcame antibiotic resistance. is shown.
However, no drugs that inhibit fatty acids are currently available to humans. “Certainly the biggest limitation is that no one can act on this information immediately,” he says Brown.
Still, the findings provide a new therapeutic target for antibiotic resistance and provide clues to how colistin works. of a completely new class [antibiotics]says Andrew Edwards of Imperial College London.
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