How fast-growing bacteria can resist antibiotics

How fast-growing bacteria can resist antibiotics Scientists have shown how certain fast-growing bacteria can be knocked down with antibiotics, according to a study published today in e-Life.

The results show that individual’s bacteria that grow rapidly within bacterial colonies show significantly higher expression of active ribosomes – molecules within the cell that make proteins. This helps the bacteria to avoid the accumulation of an important class of antibiotics called macrolides and thus resistance to treatment. These results can be used to report the development of improved antibiotic compounds targeting this survival strategy.

Bacterial infections can cause food poisoning, pneumonia, sepsis, and other serious illnesses. Although it can be treated with antibiotics, the overuse of these drugs in recent years means that bacteria are becoming more resistant to them, posing a major threat to global health.

For an antibiotic to be effective against an infection, it must reach its cellular target in a concentration sufficient to prevent bacterial growth.

How fast-growing bacteria can resist antibiotics:

“Antibiotic resistance continues to threaten the feasibility of current treatments. We have to understand how individual bacteria within a colony can prevent antibiotics from entering their cells, so we can target this mechanism with new treatments,” says Ursula Sabinska, PDRA at the University of Exeter, UK. “Most of the existing data were obtained about the permeability of drugs in bacteria by measurements take the average score from a large population or derived from a small number of bacteria. This means that little is known about the variance of the accumulation of individual drugs in many cases.

To fill this gap, Łapińska and the team began with the hypothesis that differences in how bacteria respond to drugs might be driven by the varying rates of drug transport between individual cells. To test this, the team used a multi-analytical approach, combining microfluidics and microscopy, Including bacteria that pose a threat to health – such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and an antibiotic-derived fluorescent probe by Dr. Mark Blaskowitz of the University of Queensland. This approach made the team able to examine interactions between common antibiotics and some individual live bacteria in real time, during drug dosing. By combining this approach with mathematical modeling techniques developed by Professor Krasimira Tsaneva-Atanasova of the University of Exeter, the team got data that they can use to quickly and efficiently identify individual antibiotic-resistant bacteria.

Their analyzes showed that individuals who grow up rapidly within the colony avoid the accumulation of macrolides in their cells. At the same time there is a finding that contradicts current thinking showed that slow cell growth is the primary contributor to survival without antibiotics. This avoidance is made possible by a much larger amount of ribosomes before drug treatment, compared to their slow-growing counterparts. Ribosomes activate essential cellular processes, including efflux, which is a system that pumps toxic substances, such as antimicrobial compounds, out of the cell.

Using this new knowledge, the researchers then showed that chemical treatment of the outer membrane of bacterial cells can exclude fast-growing variants that show low macrolide accumulation, which contributes to our fight against antibiotic resistance.

“This work reveals a hitherto unrecognized survival strategy in some members of bacterial colonies,” concludes Dr. Stefano Bagliara, Senior Lecturer in Microfluidics at the University of Exeter, UK. “This knowledge will directly be beneficial for microbiologists and clinicians working to develop more effective antibiotic therapies. In the long term, we hope that using our new approach in the clinical setting will help provide information for improved drug design and help us fight antibiotic resistance.”

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