Stealth technology maintains fitness after sex

Low-cost plasmids, described for the first time in the study are a threat to use of antibiotics.

Plasmids are naturally occurring 'DNA parasites' of many bacterial species and have been known about for over 30 years. Some are able to transfer themselves from one bacterial cell to another through a sex-like process called conjugation, contributing to bacterial evolution. Worryingly, as well as copying themselves plasmids can pick up and transfer bacterial genes, such as those that make pathogens resistant to antibiotics.

However, the plasmid comes at a cost to the host bacterium: gaining a plasmid can reduce the host's ability to grow and reduce its fitness. When antibiotic treatment is stopped, the new microbe–plasmid combination will be eliminated quickly through fierce competition from more 'fit', plasmid-free bacteria.

The research teams, led by Professor Charles J. Dorman at Trinity College Dublin, Ireland, and Dr John Wain at the Wellcome Trust Sanger Institute in Cambridge, UK, have discovered that an important class of plasmids use a stealth gene (called sfh) to allow entry into a new bacterium with minimal reduction in fitness.

With the low-cost version of the resistance plasmid they have described in Salmonella, resistant bacteria are likely to survive and the resistance genes to persist even if antibiotic therapy is stopped.

Their research shows that sfh codes for a protein that is very similar to another bacterial protein: the role of the protein is to organise the genetic material in bacterium and control activity of many genes, including those involved in causing disease. The sfh protein binds to the new plasmid DNA, preventing its detection by the bacterium.

"The bacterial protein, called H-NS, is a very important molecule and affects the way a bacterial pathogen operates. By bringing in its own supply of the H-NS-like stealth protein (called Sfh), the plasmid avoids interfering with the natural balance of H-NS and DNA in the cell," explained Professor Dorman.

"Our work suggests that bacterial fitness can be manipulated by altering the proportions of H-NS and DNA in the cell, perhaps through the use of drugs, an insight that may be exploited in the future to prevent or to fight infection."

Bringing its own supply of the host-like protein is clearly an advantage for the plasmid, suggesting that the normal supply of H-NS in the bacterium may become limited when new DNA is imported. If a modified plasmid, lacking the sfh gene, is transferred to Salmonella, the effects of the plasmid are very rapidly detected.

Bacteria can acquire and transfer resistance genes through a variety of methods, but this new study shows how a single gene has the potential to increase dramatically the chance of successful - and health-threatening - transfer and survival of a battery of antibiotic-resistance genes.

The consequences for managing disease - especially in developing countries - are significant, explained Dr John Wain: "These plasmids are found in many pathogenic bacteria including those that cause typhoid and paratyphoid fever. Both of these diseases are increasing in the developing world and in the UK we are seeing more and more imported cases.

"But understanding is not enough: we now need to exploit this information to try to prevent the plasmid spreading any further."

Source: Wellcome Trust Sanger Institute

Drug resistance gene has spread from East Coast to Midwest
A resistance gene that allows bacteria to beat an important class of antibiotics has started to appear in microorganisms taken from Midwestern patients, according to researchers at Washington University School of Medicine in St. Louis.
Modified mushrooms may yield human drugs
Mushrooms might serve as biofactories for the production of various beneficial human drugs, according to plant pathologists who have inserted new genes into mushrooms.
New paradigm for cell-specific gene delivery
Researchers from Northwestern University and Texas A & M University have discovered a new way to limit gene transfer and expression to specific tissues in animals. In studies to determine how plasmids enter the nuclei of non-dividing cells, the group previously identified a region of a smooth muscle cell-specific promoter that was able to mediate nuclear targeting of any plasmid carrying this sequence uniquely in cultured smooth muscle cells but in no other cell type.
Bacterial 'battle for survival' leads to new antibiotic
MIT biologists have provoked soil-dwelling bacteria into producing a new type of antibiotic by pitting them against another strain of bacteria in a battle for survival.
Researchers solve first structure of a key to intact DNA inheritance
Researchers have solved the structure of a DNA-protein complex that is crucial in the spread of antibiotic resistance among bacteria. Knowing this structure also provides fundamental insight into how cells successfully divide into two new cells with intact DNA.
Possible Chlamydia vaccine target found
U.S. scientists have identified a potential target for a vaccine to fight Chlamydia -- the world's most prevalent sexually transmitted bacterial infection.
Under magnetic force, nanoparticles may deliver gene therapy
After binding DNA segments to tiny iron-containing spheres called nanoparticles, researchers have used magnetic fields to direct the nanoparticles into arterial muscle cells, where the DNA could have a therapeutic effect. Although the research, done in cell cultures, is in early stages, it may represent a new method for delivering gene therapy to benefit blood vessels damaged by arterial disease.
Intravenous nanoparticle gene therapy shows activity in stage IV lung cancer
A cancer-suppressing gene has been successfully delivered into the tumors of stage 4 lung cancer patients via an intravenously administered lipid nanoparticle in a phase I clinical trial at The University of Texas M. D. Anderson Cancer Center. The gene, FUS1, also was found to be active in the metastatic non-small cell lung cancer tumors.

Stealth technology maintains fitness after sex

Related stories:

News discussion: