Study Shows How Bacteria Become Antibiotic Resistant

genengnews | April 24, 2019

Scientists from Denmark and Switzerland say they have shown that bacteria produce a stress molecule, divide more slowly, and thus save energy when they are exposed to antibiotics. The new knowledge is expected to form the basis for the development of a new type of antibiotic, according to the researchers. In a paper—“(p)ppGpp Regulates a Bacterial Nucleosidase by an Allosteric Two-Domain Switch”—published in Molecular Cell, a team from Aarhus University, the University of Copenhagen, and the technical university ETH Zürich in Switzerland demonstrated that bacteria quickly reduce their rate of cell division when exposed to antibiotics in order to maintain the highest possible tolerance, but rapidly start growing again when the substances are removed. “The stringent response alarmones pppGpp and ppGpp are essential for rapid adaption of bacterial physiology to changes in the environment. In Escherichia coli, the nucleosidase PpnN (YgdH) regulates purine homeostasis by cleaving nucleoside monophosphates and specifically binds (p)ppGpp. Here, we show that (p)ppGpp stimulates the catalytic activity of PpnN both in vitro and in vivo causing accumulation of several types of nucleobases during stress. The structure of PpnN reveals a tetramer with allosteric (p)ppGpp binding sites located between subunits. pppGpp binding triggers a large conformational change that shifts the two terminal domains to expose the active site, providing a structural rationale for the stimulatory effect. We find that PpnN increases fitness and adjusts cellular tolerance to antibiotics and propose a model in which nucleotide levels can rapidly be adjusted during stress by simultaneous inhibition of biosynthesis and stimulation of degradation, thus achieving a balanced physiological response to constantly changing environments,” the investigators wrote.

Spotlight

The reason for the rapid expansion and development of the therapeutic antibody sector is the capacity of monoclonal antibodies to precisely bind a target antigen and neutralise or promote its activity. The efficacy and safety.

Spotlight

The reason for the rapid expansion and development of the therapeutic antibody sector is the capacity of monoclonal antibodies to precisely bind a target antigen and neutralise or promote its activity. The efficacy and safety.

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