Genetic Engineering in the Press by GEG

No organism on earth is immune to threats, including bacteria. Phages are among their most formidable enemies, infiltrating their cells to replicate and take over. Bacteria have developed a range of strategies to counter these infections, but how they first detect an invader in their midst has long been a mystery. Researchers pioneering the study of bacterial defense systems, principally CRISPR-Cas, have focused on the immune response system of Staphylococcus schleiferi. This led them to hypothesize that these sensitive phages produce, during infection, an element that triggers activation of the cyclic oligonucleotide-based antiphage signaling system (CBASS). Next, the researchers tested various molecules produced by the bacteria or virus, including DNA, RNA and proteins. The experiment revealed that only RNA produced during a phage infection was capable of triggering an immune response. Thus, CBASS detects a specific RNA structure. The researchers then invented the newly-identified hairpin-shaped cabRNA molecule for CBASS-activating bacteriophage RNA. The molecule binds to a cyclase surface, triggering the production of a messenger molecule called cGAMP which activates the CBASS immune response. These discoveries could one day help counter the threat of antibiotic resistance.

 

Cancer immunotherapies unleash the body’s immune system to fight cancer, but microbes living in a patient’s gut can affect the outcome of those treatments, two research teams have found. Their studies, published on 2 November in Science1, 2, are the latest in a wave of results linking two of the hottest fields in biomedical research: cancer immunotherapy and the role of the body's resident microbes, referred to collectively as the microbiome, in disease.

The new University of Exeter study, published in Cell Host Microbe, shed new light on how best to combine antibiotics and phage therapy.

The researchers conducted laboratory experiments on Pseudomonas aeruginosa, a bacterium that causes disease in immunocompromised and cystic fibrosis patients. They exposed the bacteria to eight types of antibiotics and found differences in the mechanisms by which the bacteria develop resistance to phages, which affects their harmfulness. The viruses penetrate molecules on the surface of cells to infect the bacteria. In the process, the bacteria's CRISPR system learns to recognize and attack the virus in the future. However, bacteria have a second defense option. They can also modify their own cell surface to avoid infection, thereby losing the receptor to which phages normally attach. This option comes at a cost to the bacteria, and they become less virulent, which means they no longer cause disease, or the disease becomes less severe. In the study, four of the eight antibiotics tested caused a dramatic increase in CRISPR-based immunity levels. These antibiotics are all bacteriostatic, they do not kill cells directly but work by slowing cell growth.