Bacterial autolysins trim cell surface peptidoglycan to prevent detection by the Drosophila innate immune system

摘要

While most bacteria are harmless, some can cause diseases as varied as food poisoning and meningitis, so our immune system has developed various ways of detecting and eliminating bacteria and other pathogens. Receptor proteins belonging to the immune system detect molecules that give away the presence of the bacteria and trigger an immune response targeted at the invading pathogen. Peptidoglycan is one telltale molecule that betrays the presence of bacteria. Peptidoglycan is found in the bacterial cell wall, and for many years it was assumed that the immune system detected stray fragments of peptidoglycan that were accidentally shed by the bacteria. However, it was later shown that the immune system could, under certain conditions, detect peptidoglycan when it is still part of the cell wall. This raised an interesting question do bacteria use other methods to stop peptidoglycan being detected by the immune system? Now, Atilano, Pereira et al. have found that enzymes called autolysins can conceal bacteria from the receptor proteins that detect peptidoglycan. These enzymes are needed to break the bonds within the peptidoglycan present in the rigid bacterial cell wall to allow the bacteria to grow and divide. ‘Knocking out’ the genes for autolysins allowed the receptor proteins from the fruit fly, Drosophila, to bind to the bacteria; however, the mutant bacteria were able to evade the immune system after they had been treated with the purified enzymes. Atilano, Pereira et al. suggest that the autolysins trim the exposed ends of the peptidoglycan molecules on the surface of the cell wall, which could otherwise be detected by the host. The experiments also show that bacterial pathogens—including a strain of MRSA—with mutations that knock out autolysin activity trigger a stronger immune response in fruit flies, and are therefore less able to infect this host. Autolysins also help to conceal Streptococcus pneumoniae—a bacterial pathogen that is a common cause of pneumonia and infant deaths in developing countries—from detection by fruit flies. The findings of Atilano, Pereira et al. highlight how bacteria employ a number of ways to evade detection. If similar behavior is observed when bacteria infect humans, autolysins could represent a new drug target for the treatment of bacterial diseases.