Antibiotic resistance continues to be the key area of focus for a large number of researchers who are looking for a revolutionary breakthrough into the dynamics of commonly spread outbreaks. As wide-reaching literature points towards an era when millions of people could die annually from diseases that have grown resistant to even the most effective drugs, antibiotic resistance has garnered all the possibly attention of researchers.
According to a new research conducted by Science Signaling, even bacteria that don’t carry genes or mutations which lead to resistance to particular antibiotics can endure antibiotic treatment, a phenomenon known as persistence. The research indicated that Salmonella demonstrated persistence even in the full absence of toxin-antitoxin modules or (p)ppGpp production as well as under conditions that pushed intracellular adenosine triphosphate (ATP).
Researchers found that slow growth alone can cause persistence, while making it difficult to conduct treatment of some bacterial infections. The research indicated that stoppage or a slowdown in bacterial growth is a key driver of antibiotic tolerance. On the basis of diverse growth conditions and genetic contexts, the researchers found that antibiotic tolerance was contrariwise linked to the bacterial growth in Salmonella.
Though the report indicates that the growth rate is the vital indicator of persister formation in Salmonella and several bacterial species, it established that the three of TA modules, (p)ppGpp, and exposure to an acidified medium were dispensable for persister formation in different media. This further created a line of thought that Salmonella behaves like S. aureus and E. coli with regard to persister formation.
The research also highlights the conditions wherein antibiotic tolerance was achieved even when ATP was in abundance, leading to a conclusion that a low ATP concentration is essential for this property.
The model followed by the research authors accounts for the inextricable relationship between the growth and the activity of core cellular processes, both of which are the sources of biosynthetic activity and the key target areas of antibiotics. The model also indicates potential strategies to eradicate persister organisms.
Furthermore, the model sheds light on the fact that why certain antibiotic combinations boost bacterial survival, whereas others kill persister cells. This points towards the likelihood of the latter drug combination disrupting a feedback control by degrading a combination of vital core proteins that can’t be resynthesized due to inhibition of transcription. As per the researchers, three properties, including slow growth, low ATP abundance, and increased (p)ppGpp amounts play a role in persister formation as well as antibiotic tolerance.
The researchers also concluded that formation of persistent bacteria took place due to slow growth alone, despite conflicting changes in the abundance of such metabolites, proteins, and signaling molecules. As per the research findings, transitory disturbances to core activities, which are usually associated with cell growth trigger a persister state regardless of the fundamental physiological process responsible for the change in growth.
Growing cases of antibiotic resistance have led to an increased traction for antibiotic susceptibility testing, which aims to identify possible drug resistance in widely spread pathogens and to ensure susceptibility to commonly used drugs for particular infections. Large number of antibiotic sensitivity-related researches are underway, and the researchers are hopeful of finding lasting solution to the far-reaching drug-resistance problem.
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