Bacteria resistance to one antibiotic leads to resistance and to another

Antibiotics save lives, but their use also contributes to the development and spread of drug-resistant

antibiotic strains.Antibiotic-resistant bacteria infect about 2.8 million people in the U.S. each year, killing more than 35,000, according to the Centers for Disease Control and Prevention. Infections with multidrug-resistant bacteria, which are resistant to two or more antibiotics, are particularly difficult to treat.

Team experiments have shown that longexposure to one type of antibiotic essentially “primers” the bacteria. This effect has increased the likelihood that bacteria will become resistant to additional antibiotics even in the absence of further drug exposure; it also helps the strain to retain these signs of resistance for several generations.

"The effects of antibiotics appear to beindirectly selects for more stable antibiotic resistance systems. A more stable system in a strain increases the likelihood that resistance to multiple antibiotics will be acquired."

Benjamin Kerr, professor of biology at UW

Their results also show how exposureantibiotics affects the evolutionary dynamics in bacteria. This can help explain not only the increase in multidrug resistance in bacteria, but also how antibiotic resistance is maintained and distributed in the environment: in medical institutions, in soil from agricultural runoff, even long after the termination of antibiotic exposure.

Researchers tested a common mechanismthe spread of antibiotic resistance in plasmids. These are ring DNA chains that can contain many types of genes, including antibiotic resistance genes. Bacteria easily exchange plasmids even between species. Nevertheless, plasmids have their drawbacks, and past studies have shown that bacteria readily lose them.

"Even though they may carrybeneficial genes, plasmids can also interfere with many types of processes within the bacterial cell, such as metabolism or DNA replication. Thus, scientists generally consider plasmids to be expensive and burdensome to the host cell.”

Hannah Jordt, lead author of the study in biology

The university team worked with E. cellscoli containing a tetracycline resistant plasmid, and Klebsiella pneumoniae cells containing a chloramphenicol resistant plasmid. Both hosts, which were not previously grown in the presence of antibiotics, did not show great devotion to their plasmids. After nine days in an antibiotic-free medium, the proportion of Klebsiella still containing the plasmid dropped to less than 50%. For E. coli - less than 20% retained their plasmid.

When the researchers exposed the strainsantibiotics, growing each of them for 400 generations in their respective antibiotic, the strains showed a greater affinity for their plasmids even after the threat of antibiotics was removed. After nine days in an antibiotic-free medium, more than half of the E. coli and Klebsiella cells were retained with the corresponding plasmid.

“Of course, the cells needed theirplasmids to help them survive exposure to antibiotics. But even after we removed this selective pressure, both strains retained their plasmids at significantly higher levels than they had before exposure to antibiotics."

Hannah Jordt, lead author of the study in biology

In addition, other experiments showed thatexposure to antibiotics increased the occurrence of multiple Klebsiella resistance. Even without antibiotic exposure, Klebsiella pneumoniae can acquire several plasmids. For example, when researchers brought together strains carrying plasmids that did not contain antibiotics, Klebsiella and E. coli, a small fraction of Klebsiella became drug resistant, retaining their chloramphenicol resistant plasmid and acquired a tetracycline resistant plasmid from E. coli. But when the researchers repeated the experiment using bacteria exposed to antibiotics, they found about 1000 times more antibiotic-resistant Klebsiella.

Preliminary long-term exposure onlyone antibiotic, chloramphenicol, increased the likelihood that chloramphenicol-resistant Klebsiella would acquire a tetracycline-resistant plasmid from Escherichia coli in an antibiotic-free environment. In addition, the team’s experiments also showed that when antibiotic resistant cells were grown later in an antibiotic-free environment, Klebsiella chloramphenicol exposed was more easily retained by both resistant plasmids.

Researchers say evolution canexplain both the resistance of antibiotic-resistant plasmids and the increase in drug resistance in Klebsiella: exposing the strains to their corresponding antibiotic selected for mutations in their genomes to minimize conflict between the plasmid and the host, which makes it less costly to maintain this plasmid as other.