Levy and his colleagues determined that the E. coli genetically mutated four separate times in order to resist carbapenems. Specifically, the isolate removed two membrane proteins in order to prevent antibiotics from getting into the cell. The bacteria also carried a mutation of the regulatory protein marR, which controls how bacteria react in the presence of antibiotics. The isolate further achieved resistance by increasing expression of a multidrug efflux pump. Moreover, the researchers discovered that the E. coli was expressing a new protein, called yedS, which helped the drug enter the cell, but whose expression was curtailed by the marR mutation. yedS is a normally inactive protein acquired by some E. coli that affects how the drug enters the bacterial cell. It is generally expressed in bacteria through a mutation.
According to the Centers for Disease Control and Prevention, CRE germs have increased from 1% to 4% in the United States over the last decade. Forty-two states report having identified at least one patient with one type of CRE. Approximately 18% of long-term acute care hospitals in the United States and 4% of short-stay hospitals reported at least one CRE infection in the first half of 2012.
The clinical isolate of E. coli studied by Levy and his colleagues came from the sputum of a patient at Peking Union Medical College Hospital in Beijing, China, where three of the study authors are on the faculty. Drug resistance is a particularly serious public health concern in China, antibiotics are overprescribed and used widely in the livestock and farming industries.
"The first quinolone-resistant strains of bacteria came out of China, where we see that the drugs of last resort begin being used, because the other drugs don't work after so much overuse," Levy said.
|Contact: Jennifer Kritz|
Tufts University, Health Sciences Campus