A groundbreaking study from Tel Aviv University has unveiled how bacterial defense mechanisms can be neutralized, enabling efficient genetic material transfer between bacteria. This discovery holds promise for addressing the global antibiotic resistance crisis and enhancing genetic manipulation techniques for medical, industrial, and environmental applications.
The research was led by PhD student Bruria Samuel from the lab of Prof. David Burstein at the Shmunis School of Biomedicine and Cancer Research, Wise Faculty of Life Sciences, Tel Aviv University. The team also included Dr. Karin Mittelman, Shirly Croitoru, and Maya Ben-Haim. Their findings were published in the prestigious journal Nature (Diverse anti-defense systems are encoded in the leading region of plasmids).
Genetic diversity is vital for species to adapt to environmental changes. In humans and many organisms, sexual reproduction drives this diversity. However, bacteria lack such a mechanism. Instead, they rely on alternative strategies, such as direct DNA transfer, to maintain genetic variation. This process plays a key role in their rapid adaptation, exemplified by the alarming spread of antibiotic resistance.
One primary method bacteria use for DNA transfer is conjugation, where one bacterium directly connects to another through a microscopic tube to transfer genetic material known as plasmids. Prof. Burstein explains, “Plasmids are small, circular DNA molecules classified as ‘mobile genetic elements.’ Unlike viruses, plasmids transfer between bacteria without killing their hosts.”
Plasmids often carry advantageous traits, such as antibiotic-resistance genes. However, bacteria possess defense systems designed to destroy foreign DNA, including plasmids. “While conjugation and bacterial defense mechanisms are well-known, the exact way plasmids evade these defenses remained unclear until now,” says Prof. Burstein.
Bruria Samuel began her research by analyzing 33,000 plasmids using computational tools. She identified genes linked to ‘anti-defense’ systems, which help plasmids bypass bacterial defense barriers. Notably, these genes were consistently located near the DNA cut site—the point where one strand of the plasmid is cleaved and transferred during conjugation. This strategic positioning ensures these anti-defense genes are the first to enter the recipient bacterium, neutralizing its defense systems immediately.
Prof. Burstein recalls his initial disbelief upon seeing Samuel’s results, noting that no previous research had observed this phenomenon. To validate their findings, the team conducted laboratory experiments using plasmids carrying antibiotic resistance genes and bacteria equipped with the CRISPR defense system. They demonstrated that when anti-defense genes are positioned near the entry site, plasmids successfully bypass CRISPR defenses, allowing the recipient bacteria to become antibiotic-resistant. Conversely, when these genes are located elsewhere, the defense system destroys the plasmid, and the bacteria die.
This discovery opens exciting avenues for future research and applications. Understanding how anti-defense genes are positioned on plasmids could lead to the identification of new anti-defense genes and improve plasmid design for genetic manipulation. Prof. Burstein highlights potential applications, such as developing plasmids to block antibiotic resistance genes in hospital environments, teaching bacteria to degrade pollutants in soil and water, and optimizing gut bacteria for human health benefits.
Dr. Ronen Kreizman, CEO of Ramot, Tel Aviv University’s technology transfer company, emphasizes the biotechnological significance of this discovery. “This breakthrough could revolutionize fields like drug development, synthetic biology, agriculture, and environmental technology. By fine-tuning genetic material transfer, we can address pressing global challenges. Ramot is actively working to commercialize this technology and unlock its full potential.”
This study not only sheds light on a fundamental bacterial process but also paves the way for innovative solutions to some of today’s most critical health and environmental issues.
