C. difficile is a unique type of bacterium, that has its cell components protectively shielded from the outer world by tightly-packed molecules. This characteristic feature of this bacterium has made it immune to all kinds of antibiotics, and for several years has been known to be linked to infection of the intestines causing effects ranging from diarrhea to death. It has been observed that the intake of antibiotics as a means to fight this unique bacterium, only worsened the effect, as the antibiotics do not penetrate the coating (S-layer) of the bacterium. Instead, they (antibiotics) act on the healthy bacteria in the body, killing them and putting the infected human in more danger.
However, after more than ten years of studying this bacterium, the team of scientists from Newcastle, Sheffield, and Glasgow Universities, led by Dr. Paula Salgado, in collaboration with scientists from Imperial College and Diamond Light Source, have finally answered the “how” question regarding the packing molecules of the S-layer of the C. difficile bacterium.
The study reveals a clear picture of the protective coating of the bacterium. They describe this flexible layer as a mesh of tightly-packed protein (SlpA) molecules, that are closely linked together in a way that makes the layer very selectively semi-permeable, allowing only a few molecules to pass through it and access the bacterium’s cells.
To determine the structure of the protein, they needed to study the arrangement of the crystalline molecules that make up the protein. They employed X-ray and electron crystallography to achieve this; however, these techniques only allowed for the study of a 2D view of the molecules. Therefore, to configure the molecules to mimic a 3D one, they made use of the Diamond synchrotron. Using I24, the microfocus beamline, they tested hundreds of the crystals to collect the best data. Thanks to the scientists at Diamond Light Source, models (from the sulfur atoms of the protein molecules) were built using the long-wavelength I23 beamline. The models were important to allow for easy determination of the structures. This made the team able to finally get a clearer picture of the structure of the SlpA protein that formed the outer protective layer of the bacterium.
The team is currently working on modifying the study to invent new treatment methods to tackle C. difficile infection – special C. diff drugs that can penetrate its protective coating and fight infections.
The findings from this study are of high clinical value as they have unraveled the key component to tackling one of the top 10 public health threats affecting humanity – antimicrobial resistance, AMR (as stated by the WHO).
With the revelation from this study, scientists now have a better war strategy in the fight against the increasing bacterial resistance to antibiotics, as it has opened the room for the production of drugs that can penetrate whatever shield-like outer coating of bacteria.
Finally, the way around the once-considered “indomitable” C. difficile and its likes have been discovered, and soon, drugs that can subdue them would be manufactured. Thanks to the scientists who dedicated their time, efforts, and resources to the discoveries from this study.