The findings, published in the July 15 issue of Molecular Cell, have implications for addressing the global threat of antibiotic resistance, and are especially concerning because they could complicate the development of new antibiotics and contribute to the spread of resistance genes among multiple species of bacteria.
"The rise in antibiotic resistance is one of the most pressing health challenges of our time," said Victor Nizet, MD, professor and vice-chair of the Department of Pediatrics and the Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego School of Medicine. "Our discovery uncovers a mechanism by which resistance genes are shared among different types of bacteria, providing new insights into the evolution and spread of resistance to life-threatening bacterial infections."
Nizet is a member of the Molecular Biology of Bacterial Infections Training Program at UC San Diego and senior author of the study. First author is Justin Silpe, PhD, a research scientist in Nizet's lab.
Transferring Resistance Genes
The spread of antibiotic resistance genes is a major public health problem. In the United States, the Centers for Disease Control and Prevention (CDC) reports that at least 2 million people get antibiotic-resistant infections, and at least 23,000 of those people die, each year.
Bacteria can naturally acquire genes that confer resistance to certain antibiotics. However, in recent decades, the spread of antibiotic resistance has been accelerated by the overuse and misuse of antibiotics in humans and animals. This has created a selective pressure that favors the survival and spread of resistant bacteria.
Bacteria can transfer resistance genes to other bacteria through various mechanisms, including horizontal gene transfer (HGT). One common form of HGT is called conjugation, which involves the transfer of genes from one bacterium to another through direct contact.
The newly discovered mechanism of HGT identified by the UC San Diego researchers is different from conjugation. It involves the transfer of genes from one bacterium to another through the release of membrane vesicles. These vesicles are small, spherical structures that are released from the outer membrane of bacteria.
The researchers found that membrane vesicles released by one type of bacteria can be taken up by other types of bacteria, including those that are not closely related. This process can transfer resistance genes from one species of bacteria to another, even if the two species are not in direct contact.
Broad Implications for Antibiotic Resistance
The discovery of this new mechanism of HGT has broad implications for antibiotic resistance. It suggests that resistance genes can be transferred more easily and widely among different types of bacteria than previously thought. This could make it more difficult to develop new antibiotics that are effective against all types of resistant bacteria.
"Our findings reveal a previously unrecognized mechanism for the transfer of resistance genes between bacteria," said Silpe. "This could contribute to the spread of antibiotic resistance among multiple species of bacteria, making it more challenging to treat infections caused by these resistant bacteria."
The researchers emphasized the need for further research to understand the prevalence and significance of this new mechanism of HGT in the spread of antibiotic resistance. They are also investigating ways to inhibit the transfer of resistance genes through membrane vesicles, as a potential strategy to combat antibiotic resistance.
The research team included scientists from the University of California, San Diego School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. The study was funded by the National Institutes of Health (R01AI113039).
