Can bacterial growth rate influence the effectiveness of antibiotics?

Can bacterial growth rate influence the effectiveness of antibiotics?

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According to new research published by eLife, it appears so. The work, led by Urszula Łapińska and Stefano Pagliara from the University of Exeter, shows that some fast-growing bacteria can resist antibiotics. But, how? Allegedly, ribosomes, the machinery that produces proteins within the cell, are the key.

Bacterial infections can cause anything from mild discomfort to serious health complications and even death. The introduction of antibiotics has greatly reduced the death burden from bacterial diseases. However, antibiotic resistance threatens to leave bacterial infections without effective treatment, posing a significant risk to global health. Actually, in 2019, 1.27 million deaths worldwide were directly attributable to antibiotic-resistant bacteria. Therefore, it is imperative to elucidate the mechanisms that provide these microorganisms with an advantage against antibiotics.

To this end, Łapińska, Pagliara, and their team followed the individual response of genetically similar Escherichia coli bacteria to antibiotics. And what they observed was somewhat surprising: faster-growing microorganisms were able to survive better. Closer examination revealed that these bacteria had a higher number of ribosomes, which could help eliminate toxic compounds.

Many antibiotics, such as macrolides, a class of compounds to which erythromycin belongs, need to accumulate inside bacteria to a certain concentration to act against their target and be effective. They usually use channel-like structures (pores) or pumps to enter the bacterial cells. However, these gateways could also become exit gates, in fast-growth bacteria with numerous ribosomes that can both augment the number of pores and the processes that pump antibiotics out of the cell. To test this hypothesis, researchers manipulated bacteria to erase this advantage and microorganisms developed sensitivity to antibiotics.

«These data support the need to characterize the unique mechanisms of accumulation of each antibiotic compound to understand and combat bacterial resistance. There is an urgency to develop new strategies to fight this menace», says Roberto Díez, CEO of Telum Therapeutics. «However, antibiotics are not the only antibacterial compounds and in recent years, research on endolysins has advanced significantly. These phage-derived lytic enzymes degrade the peptidoglycan layer lining the bacterial cell wall, which destroys the bacteria. Moreover, they target specific bacterial strains, causing little harm to the surrounding microbiome, lack a mechanism of bacterial resistance, and can be engineered to enhance their antimicrobial properties». Therefore, they are a must-have in the future of bacterial disease treatment.

Article of reference

Urszula Łapińska, Margaritis Voliotis, Ka Kiu Lee, Adrian Campey, M Rhia L Stone, Brandon Tuck, Wanida Phetsang, Bing Zhang, Krasimira Tsaneva-Atanasova, Mark AT Blaskovich, Stefano Pagliara. Fast bacterial growth reduces antibiotic accumulation and efficacy. eLife 11:e74062, 2022.

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