HomeScience and ResearchScientific ResearchThis New Insight Could Be The Key to Overcoming Antimicrobial Resistance

This New Insight Could Be The Key to Overcoming Antimicrobial Resistance

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Researchers have discovered new info on how bacteria connect to swap DNA that helps them withstand drugs.

One of the most common ways for dangerous bacteria to develop antibiotic resistance is to get DNA from bacteria that are already resistant. This DNA transfer is accomplished through a process known as conjugation, which is similar to bacterial sex, in which two bacteria develop an intimate bond and one donates a packet of DNA to the other.

This is critical because antibiotic resistance is causing diseases that were once curable to become fatal. According to the O’Neill analysis, which was commissioned by the UK government, by 2050, 10 million fatalities could be due to antibiotic-resistant bacterium infection. If researchers could better comprehend the molecular underpinnings of bacterial conjugation, they might be able to create novel strategies that inhibit the proliferation of antibiotic resistance.

Much study has been done to show how two bacterial cells initially contact one other in preparation for transfer since the discovery of bacterial conjugation in the 1940s. However, the process by which donor and recipient bacteria formed the close bonds that allowed for effective DNA transfer remained a mystery.

The proteins that enable these intimate connections have now been discovered by a team lead by Imperial College London researchers. Nature Microbiology published the findings today.

The new information may also aid scientists in forecasting the development of developing resistance among bacterial infections, as it explains why some DNA packets known as plasmids are prevalent in specific bacterial species.

“The spread of antimicrobial resistance is an acute problem affecting human health globally, and we urgently need new tools to fight it,” says lead researcher Professor Gad Frankel of Imperial College’s Department of Life Sciences and the MRC Centre for Molecular Bacteriology and Infection.

“Understanding, and ultimately interrupting, the process by which bacteria share their abilities to evade antimicrobial drugs will go a long way to helping stall the spread of resistance,” adds the researcher.

Plasmids are DNA packets that reside inside bacterial cells and multiply independently of the chromosomal DNA. They have a modest number of genes that can encode for a variety of roles, including antimicrobial drug resistance.

During conjugation, the scientists discovered that a protein from the donor bacterium called TraN serves as a ‘plug’ to connect itself to a specific outer membrane receptor, or’socket,’ in recipient bacteria. Plasmids shared by conjugation express one of four TraN variations, each of which binds to a distinct outer membrane receptor in the recipient bacteria, allowing for effective plasmid transfer from one cell to the next.

Imperial researchers collaborated with colleagues at the University of Virginia in the United States to visualize the intimate attachment process using high-power cryo-electron microscopy, as well as structural biologists from Imperial. The researchers examined the TraN proteins of numerous resistance plasmids and the recipient bacterium receptors for several key human bacterial infections using recent breakthroughs in artificial intelligence and bioinformatics.

“These protein-receptor pairings explain conjugation species-specificity,” says first author Wen Wen Low of Imperial College’s Department of Life Sciences and the MRC Centre for Molecular Microbiology and Infection. “Using plasmid datasets from Enterobacteriaceae – a family of bacteria that include Salmonella and E. coli,” adds the first author, “we showed how our classification reflects the real-world distribution of resistance plasmids .”

“These findings present a key advancement in understanding how conjugative mating pairs are formed and will allow us to predict the spread of emerging resistance plasmids into high-risk bacterial pathogens,” adds co-author Dr Konstantinos Beis of Imperial College London’s Department of Life Sciences and Harwell Research Complex in Oxfordshire.

The researchers are still looking at the details of TraN’s interactions with receptors, such as what drives plasmid specialization and how conjugation dynamics and preferences play out in mixed microbial communities. They hope that this research will pave the way for new techniques to combat antibiotic resistance.

Image Credit: Imperial College London

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