“Bacterial sex” plays an important role in the spread of antibiotic resistance. Researchers have now gained new insights into the mechanisms of this genetic exchange: they have been able to identify components of the system that mediate close contact between certain types of bacteria. The new findings could help to develop measures to curb the spread of antibiotic resistance, say the scientists.
“You have become infected with a multi-resistant germ” is a feared diagnosis that is becoming more and more common. Many bacterial pathogens can no longer be killed by common antibiotics because they are insensitive to the effects of these substances. This trait is based on genetic peculiarities that bacteria have developed in the course of “breeding” under the pressure of the massive use of antibiotics. A particular problem is that the resistant germs not only pass on their resistance genes to their offspring, but can also transmit them to other bacteria. This DNA exchange takes place via what is known as conjugation – a process that is comparable to sex.
Two bacteria form an intimate bond with one another and one of the two then transfers genetic material to the other. The donor bacterium first forms a thread-like structure to make contact with the recipient – then the two then “snuggle up” to each other. In this case, bridge structures are formed at the contact points. So-called plasmids are then transferred via these: DNA structures that are found in bacterial cells but reproduce separately from the main genetic material of the microbes. They carry a small number of genes that code for specific functions – including resistance to antimicrobial drugs. Because of this importance, bacterial conjugation has been the focus of research for some time.
How does “bacterial sex” work?
The process by which two bacterial cells first come into contact with one another is considered comparatively well researched. However, the researchers led by Wen Wen Low of Imperial College London have now shed light on the mechanism by which donor and recipient bacteria form the close bond that ultimately enables DNA transfer. Their results are based on examining the conjugation processes in certain types of bacteria, including salmonella and pneumonia pathogens. In order to make the intimate attachment processes visible, the researchers carried out special electron microscopic analyses. In addition, structural biological methods were used to gain insight into the protein building blocks that play a role in the processes. The team also used artificial intelligence and bioinformatics to elucidate specific functions of these proteins.
The researchers found that during conjugation, a special protein in the donor bacterium acts as a ‘cone’ to attach to a specific receptor or ‘slot’ in the outer membrane of the recipient bacterium. The cone protein, called TraN, is formed from genetic information that is on the plasmid of the donor bacterium. The scientists were also able to show that plasmids that are passed on by conjugation express one of four variants of the protein TraN. Each version also binds to a specific receptor on the outer membrane of the recipient bacterium. The results show that it is only this compatibility that enables efficient transfer of plasmids from one cell to another.
Why who mates with whom
“These protein-receptor pairings explain the species specificity of the conjugation. Using plasmid datasets from Enterobacteriaceae – the family of bacteria that also includes Salmonella or E. coli – we have shown how our classification reflects the real distribution of resistance plasmids,” says Low. His colleague Konstantinos Beis continues: “These results represent an important advance in understanding the formation of conjugative pairings and will allow us to predict the spread of emerging resistance plasmids in high-risk bacterial pathogens.”
The findings could therefore also offer possible approaches to developing measures that curb the spread of antibiotic resistance, say the scientists. “The spread of antimicrobial resistance is an acute problem affecting human health worldwide and we urgently need new tools to combat it. If we can understand, and ultimately disrupt, the process by which bacteria share their abilities to evade antimicrobial drugs, we can go a long way in halting the spread of resistance,” says senior author Gad Frankel of Imperial College London. The team therefore now wants to stay on the ball: The researchers want to further elucidate the interactions of TraN and the receptors.
Source: Imperial College London, Nature Microbiology, doi: 10.1038/s41564-022-01146-4