New Insights May Empower Phages to Combat Antibiotic-Resistant Bacteria

Key Takeaways

  • Researchers at the University of Southampton discovered how bacteria defend against phages, offering insights into combating antibiotic resistance.
  • The bacterial defence mechanism, called Kiwa, functions like a security system that can be tricked by certain phages through a decoy protein.
  • Over 600 types of phages have been identified, with ongoing efforts to collect samples from the public to enhance phage research.

New Insights into Bacterial Defences

Researchers at the University of Southampton have made significant strides in understanding bacterial defenses against viruses known as phages, crucial information as the fight against antibiotic resistance intensifies. Phages are viewed as a viable alternative to traditional antibiotics and target only bacteria without affecting human cells.

Published in the journal Cell, this research explores a key bacterial defense mechanism named Kiwa. Dr Franklin Nobrega, an Associate Professor at the university, likens Kiwa to a guardian in Māori mythology, underscoring its role in protecting bacteria from phage attacks. Using advanced imaging techniques, the team examined how Kiwa operates at the molecular level, discovering that it consists of two components—KwaA and KwaB. Together, they form a protective barrier akin to chainmail that detects and disrupts the entry of phage DNA into the bacterial cell.

When a phage attempts to attach, KwaA acts as a sensor, activating KwaB, which then binds to and deactivates the phage DNA before it can hijack the cell’s machinery. However, some phages have developed a counter-strategy by releasing a ‘decoy’ protein called Gam that misleads KwaB into attacking it, allowing the true phage DNA to penetrate the bacterial defenses.

Despite the ingenuity of phages, Kiwa represents just one of several defense mechanisms utilized by bacteria, including another system known as RecBCD, designed to counter phage DNA as well. When both systems are activated in tandem, they create an effective barrier that phages struggle to breach.

Dr Nobrega emphasized the ongoing evolutionary arms race between phages and bacteria, comparing it to how hackers attempt to bypass security systems. As bacteria continually adapt and enhance their defenses, understanding these mechanisms is critical to finding ways to combat the rising threat of antibiotic resistance, which is projected to claim ten million lives annually by 2050 and costs the NHS around £180 million each year.

To further this research, the University of Southampton is actively collecting phage samples, focusing on over 600 different types identified so far. They are encouraging the public to contribute samples from contaminated water sources, which harbor both bacteria and phages, aiding in the discovery of phages capable of overcoming bacterial defenses.

Dr Nobrega states that by deepening the understanding of these defense systems, researchers can better identify potential weaknesses and select the most effective phages for therapeutic use. The more samples collected, the higher the likelihood of uncovering phages with the greatest potential for success.

The findings, described in the paper titled “Kiwa is a membrane-embedded defence supercomplex activated at phage attachment sites,” are pivotal in guiding future strategies in the fight against antibiotic-resistant bacteria. The research received funding from several organizations, including The Royal Society, and is supported by the NIHR Southampton Biomedical Research Centre.

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