Scientists show how fast-growing bacteria can resist antibiotics

Individual E. coli cells show a dramatically different accumulation of antibiotics. Credits: UlaŁapińska

According to one study, scientists have demonstrated how fast-growing bacteria can be retreated with antibiotics. Was announced in eLife.

The results show that fast-growing individuals in bacterial colonies show significantly higher expression of active ribosomes, which are intracellular particles that synthesize proteins. This helps the bacteria avoid the accumulation of an important class of antibiotics called macrolides and therefore resists treatment. These findings can be used to signal the development of improved antibiotic compounds targeting this survival strategy.

Bacterial infectious diseases can cause food poisoning, pneumonia, sepsis and other serious illnesses. Although they can be treated with antibiotics, the abuse of these drugs in recent years means that the bacteria are becoming more and more resistant to them, pose a significant threat to the health of the world.

For an antibiotic to be effective against infection, it must reach its cellular target at a concentration sufficient to inhibit the growth of the bacterium.

“Antibiotic resistance continues to threaten the feasibility of current therapies. It is necessary to understand how individual bacteria in a colony can prevent antibiotics from entering cells. That way, new therapies can target this mechanism, “said UrszulaŁapińska, PDRA, University of Exeter. “Most of the existing data on bacterial drug permeability were obtained by mean results from large populations or by measurements derived from a small number of bacteria. This is a large number of simple bacterial colonies. It means that little is known about the variability of individual drug accumulation across a cell. ”

To address this gap, Łapińska and his team began with the hypothesis that changes in the way bacteria respond to drugs can be caused by changes in drug transport rates between individual cells.To test this, the team used a multi-analytical approach to microfluidics-microscopy, a bacterium that poses a health threat, ie. E. coli, Pseudomonas aeruginosa, Burkholderia Seno Sepasia When Staphylococcus aureus Antibiotic-derived fluorescent probe by Mark Blaskovich of the University of Queensland.

This approach allowed the team to study the interactions between common antibiotics and many living individual bacteria in real time during drug administration. By combining this approach with a mathematical modeling technique developed by Krasimira Tsaneva-Atanasova at the University of Exeter, the team obtained data that could be used to quickly and efficiently identify individual antibiotic-resistant bacteria.

Their analysis showed that fast-growing individuals within the colony avoid the accumulation of intracellular macrolides. This is in contrast to the current belief that slow cell growth is the main cause of survival for genetically mutated antibiotics. This avoidance is made possible by the significantly higher amount of ribosomes before drug treatment compared to the slow-growing counterparts of the individual. Ribosomes enable important cellular processes, including excretion, which is a system that excretes toxic substances such as antibacterial compounds from cells.

Second, this new knowledge can be used to chemically manipulate the outer membrane of bacterial cells to eradicate fast-growing mutants with low macrolide accumulation and help fight antibiotic resistance. Was shown.

“This study reveals an unrecognized survival strategy in some members of the bacterial colony,” concludes Stefano Pagliara, senior lecturer at Microfluidics at the University of Exeter. “These insights directly benefit microbiologists and clinicians working on the development of more effective antibiotic therapies. In the long run, they have been improved by using new approaches in the clinical setting. We hope to inform you about drug design and help you fight antibiotic resistance. “

Reissued with the kindness of eLife.