The sticky outer layer of fungi and bacteria, called the “extracellular matrix” or ECM, has the consistency of jelly and acts as a protective layer and shell. But according to a recent study in the journal iScience, conducted by the University of Massachusetts Amherst in collaboration with Worcester Polytechnic Institute, the ECM of some microorganisms forms a gel only in the presence of oxalic acid or other simple acids. Because ECM plays an important role in everything from antibiotic resistance to clogged pipes and contamination of medical devices, understanding how microorganisms manipulate their sticky gel layers has broad implications for our daily lives.

        “I’ve always been interested in microbial ECMs,” said Barry Goodell, professor of microbiology at the University of Massachusetts Amherst and senior author of the paper. “People often think of the ECM as an inert protective outer layer that protects microorganisms. But it can also serve as a conduit for nutrients and enzymes in and out of microbial cells.”
       The coating serves several functions: its stickiness means that individual microorganisms can clump together to form colonies or “biofilms”, and when enough microorganisms do this, it can clog pipes or contaminate medical equipment.
       But the shell must also be permeable: many microorganisms secrete various enzymes and other metabolites out through the ECM, into the material they want to eat or infect (such as rotten wood or vertebrate tissue), and then, once the enzymes have completed their work, the task of digestion – return nutrients back through the ECM.
        This means that ECM is not just an inert protective layer; In fact, as Goodell and colleagues demonstrated, microorganisms appear to have the ability to control the viscosity of their ECM and therefore its permeability. How do they do it?
        In fungi, the secretion appears to be oxalic acid, a common organic acid that occurs naturally in many plants, and, as Goodell and his colleagues discovered, many microorganisms appear to use the oxalic acid they secrete to bind to external layers of carbohydrates. forming a sticky substance. , jelly-like ECM.
        But when the team looked closer, they discovered that oxalic acid not only helped produce ECM, but also “regulated” it: the more oxalic acid the microbes added to the carbohydrate-acid mixture, the more viscous the ECM became. The more viscous the ECM becomes, the more it blocks large molecules from entering or leaving the microbe, while smaller molecules remain free to enter the microbe from the environment and vice versa.
        This discovery challenges traditional scientific understanding of how the different types of compounds released by fungi and bacteria actually get from these microorganisms into the environment. Goodell and colleagues suggested that in some cases microorganisms may have to rely more on the secretion of very small molecules to attack the matrix or tissue on which the microorganism depends to survive or become infected. This means that secretion of small molecules may also play a large role in pathogenesis if larger enzymes cannot pass through the microbial extracellular matrix.
        “There appears to be a middle ground,” Goodell said, “where microorganisms can control acidity levels to adapt to a particular environment, retaining some of the larger molecules, such as enzymes, while allowing smaller molecules to easily pass through the ECM. “Modulation of the ECM with oxalic acid may be a way for microorganisms to protect themselves from antimicrobials and antibiotics, since many of these drugs consist of very large molecules. It is this customization ability that could be the key to overcoming one of the major obstacles in antimicrobial therapy, as manipulating the ECM to make it more permeable could improve the effectiveness of antibiotics and antimicrobials.

       “If we can control the biosynthesis and secretion of small acids such as oxalate in certain microbes, then we can also control what goes into the microbes, which could allow us to better treat many microbial diseases,” Goodell said.
       In December 2022, microbiologist Yasu Morita received a grant from the National Institutes of Health to support research ultimately aimed at developing new, more effective treatments for tuberculosis.

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