Tag: phages

New Bacteriophage Could Combat C. Diff

A bacteriophage. Credit: NIAH

A group of newly discovered bacteriophages named after the UK village of Colney could help combat C. difficile infections.

Clostridioides difficile, or C. diff, is a species of bacteria that infects the human gut. It can become a major problem when our normal gut microbes are impaired, most commonly during a course of antibiotics. This leads to an overgrowth of C. diff, with toxins it produces causing diarrhoea and severe inflammation.

Treatment involves further courses of antibiotics, but relapse and recurrent infections are common. The strains are becoming more resistant to antibiotics and causing more severe illness.

This prompted researchers in Norwich to look for the bacteria’s natural enemy, bacteriophages. They screened 27 different C. diff strains for any bacteriophages, finding one, which they called ΦCD27 (phiCD27). Genome sequencing confirmed this phage had not been discovered before. In fact, the members of the International Committee on Taxonomy of Viruses (ICTV) decided it was genetically distinct enough to form a new group, or genus of phages.

The ICTV decided to name the new genus Colneyvirus, the Colney parish address of the Institute of Food Research (IFR, now part of Quadram Institute), where it was first discovered.

Like normal viruses, phages reproduce by injecting their genetic material into bacteria, making viral copies using the host’s own machinery. Using enzymes called endolysins, they destroy the bacterial cell wall and escape.

The researchers extracted the gene for ΦCD27’s endolysin and put it into another bacterium, E. coli so that they could produce and purify the endolysin. It was proven active against 30 different C. diff strains, including hypervirulent strains behind the current epidemic. It also didn’t affect other common bacterial species in the human gut microbiome.

”This phage and the endolysin encoded by its genome can provide a targeted approach to combat C. diff infections, in contrast to use of broad spectrum antibiotics that cause collateral damage by inhibiting other members of the gut bacterial population” said Professor Arjan Narbad, Group Leader at the Quadram Institute.

However, to be effective the endolysins need to be delivered into the gut, so the team also put the gene into a strain of lactic acid bacteria that has previously been used to deliver proteins and vaccines to the gut.

The research team believes this could serve as the basis for future new treatments C. diff. The system needs more work, but in the battle against this bacterial pandemic, the colneyvirus could be a vital ally.

Source: Quadram Institute

Harnessing Tailocins, Antibacterial ‘Homing Missiles’

A Berkeley Lab-led team is investigating how to harness tailocins, antibacterial nanomachine ‘weapons’ akin to phages but produced by certain bacteria in suicide attacks against other strains.

“Tailocins are extremely strong protein nanomachines made by bacteria,” explained Vivek Mutalik, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) who studies tailocins and phages, the bacteria-infecting viruses that tailocins appear to be remnants of. “They look like phages but they don’t have the capsid, which is the ‘head’ of the phage that contains the viral DNA and replication machinery. So, they’re like a spring-powered needle that goes and sits on the target cell, then appears to poke all the way through the cell membrane making a hole to the cytoplasm, so the cell loses its ions and contents and collapses.”

Many bacteria can produce tailocins, seemingly under stress conditions. However, the tailocins are only lethal to specific strains, and seem to be used by bacteria to compete with rivals. Since they are so similar to phages, scientists believe that tailocins are repurposed from DNA that was injected into bacterial genomes from viral infections.

According to Mutalik, tailocins kill the bacteria that produce them as they erupt through the membrane, much the way replicated viruses do. However, once released, the tailocins selectively target certain strains and not the host lineage cells.

“They benefit kin but the individual is sacrificed, which is a type of altruistic behavior. But we don’t yet understand how this phenomenon happens in nature,” Mutalik commented. Scientists also don’t know precisely how the stabbing needle plunger of the tailocin functions.

These topics, and tailocins as a whole, are an area of hot research due to the many possible applications. Mutalik and his colleagues in Berkeley Lab’s Biosciences Area along with collaborators at UC Berkeley are interested in harnessing tailocins to better study microbiomes. Other groups are keen to use tailocins as an alternative to traditional antibiotics -which indiscriminately wipe out beneficial strains alongside the bad and are increasingly ineffective due to the evolution of drug-resistance traits.
There is also great interest in using tailocins as an alternative to antibiotics, due to increasing antibiotic resistance and the fact that conventional antibiotics wipe out beneficial strains along with the disease-causing ones.

In their most recent paper, the collaborative Berkeley team explored the genetic basis and physical mechanisms governing how tailocins attack specific strains, and looked at genetic similarities and differences between tailocin producers and their target strains.

Upon examination of 12 strains of tailocin-using soil bacteria, the researchers found that differences in the lipopolysaccharides on the outer membranes determined whether they were targeted by a particular tailocin.

“The bacteria we studied live in a challenging, resource-poor environment, so we’re interested to see how they might be using tailocins to fight for survival,” said co-lead author Adam Arkin, a senior faculty scientist in the Biosciences Area and technical co-manager of the Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA) Scientific Focus Area. Arkin observed that although bacteria can easily be induced to produce tailocins in the lab, as well as scale up for mass production for medicinal applications, it is not well understood how bacteria deploy tailocins in their natural environment, and how or why particular strains are so precisely targeted.

“Once we understand the targeting mechanisms, we can start using these tailocins ourselves,” Arkin added. “The potential for medicine is obviously huge, but it would also be incredible for the kind of science we do, which is studying how environmental microbes interact and the roles of these interactions in important ecological processes, like carbon sequestration and nitrogen processing.”

At the moment, it is difficult to observe what is happening in a bacterial community, but tailocins could remove individual strains with precision to allow a better understanding of the situation.

Follow-up studies being conducted involve taking atomic-level images of the taolicins in action.

Source: SciTech Daily

Journal information: “Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins” by Sean Carim, et al., 1 March 2021, The ISME Journal. DOI: 10.1038/s41396-021-00921-1