Researchers at the Hebrew University of Jerusalem have for the first time worked out how even non-antibiotic resistant bacteria survive antibiotic treatment. The study, which was published this week in the journal Nature Communications, could pave the way for improved therapies for treating bacterial infection.

A petri dish with bacteria culture (illustrative) – Photo: Dreamstime

The problem of bacterial resistance to antibiotics has preoccupied many scientists for years. Aside from bacteria that have undergone mutations, making them resistant to antibiotics, another kind of bacterium exists as well, which is inherently unaffected by antibiotic treatment, called “persistent bacteria.”

“Among every group of bacteria that responds to antibiotic treatment, there is a small group of bacteria that is unaffected by the treatment, even though they have no inherent resistance to antibiotics,” explains Prof. Gadi Glaser of the Hebrew University of Jerusalem medical school and department of developmental biology and cancer research.

According to Glaser, these persistent bacteria survive antibiotic treatment because they are “inactive” during the treatment, and thus avoid its effects. They comprise 1 percent of all bacteria, although even that small amount is enough to cause reinfection after antibiotic treatment.

Until now, it was known that there was a connection between these “inactive” bacteria, and a toxin called HipA, which is present in the body. It was unclear however, what exactly triggered the toxin, which is what causes the bacteria to become unaffected by antibiotic treatment. Now, Glaser and Prof. Nathalie Balaban of the university’s Racah Institute of Physics have succeeded in understanding the biological mechanism that causes the bacteria to become inactive.

Their research found that the ineffectiveness of antibiotics is indeed caused by the HipA toxin, which disrupts the messaging process necessary for antibiotics to properly function. The toxin harms the tRNA molecules, which regulates the connection between the amino acid glutamie, and the protein itself. “As soon as the toxin disrupts the communication, the essential materials cannot get into the protein, creating a situation in which there is tRNA running free in the cell. This causes the bacteria to become inactive – effectively making it unaffected by antibiotics,” says Glaser.

Balaban’s lab contains an advanced scanning system that was used to examine dozens of petri dishes, photographed every ten minutes, which allowed for accurate documentation of the “inactive” bacteria’s development. “The bacteria go into a state of ‘hunger’ even before there is a real lack of nutrients. It’s like an investor that sells their stock in the market based only on an assumption, before its value drops,” says Balaban.

“When you treat using antibiotics, there will always be some bacteria that survive. If we manage in the future to introduce a substance that deals with the biological mechanism that the study uncovered, antibiotics will be more effective,” says Glaser.

The study was conducted at Glaser’s lab by doctoral candidate Ilana Kaspy, and in Balaban’s lab by doctoral candidates Eitan Rotem and Noga Weiss and by Dr. Irine Ronin.

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