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How Bacteria Support Wound Healing

The skin is the human body

source : www.miragenews.com

The skin is the largest organ of the human body.

Source: Wikimedia Commons

Although they were not recognized as pathogens until the late 19th century, the harmful effects of bacterial infections have been known to humans for thousands of years. Some have even become mythical; for example, during the American Civil War (1861-1865), flesh wounds that ‘glow’ in the dark were thought to have a lower risk of infection and a better chance of healing. The origins of this folklore are unclear, but accounts point to the Battle of Shiloh (1862), in which more than 16,000 soldiers were injured in the cold Tennessee mud while waiting for field medics – the perfect conditions for shrapnel and dirt to spread infections in their to cause wounds. .

Exactly why some wounds would have glowed, and what the glow might have to do with healing, remained a mystery until 2001, when two high school students presented their work at the Intel International Science and Engineering Science Fair. Their research, supported by the USDA Agricultural Research Service, found a bioluminescent insect pathogen Photorhabdus luminescens could have survived in the wounds of soldiers with hypothermia, where they might have produced antibiotics that can inhibit the growth of other infection-causing bacteria. The microbes also glow a cool blue, earning the folkloric nickname “Angel’s Glow.” P. luminescens-infected wounds. Although hard evidence for Angel’s Glow at Shiloh is scarce, a text from 40 years ago describes a “slight phosphorescence from a light wound in the leg” that occurred during the siege of Mannheim in Germany (1795), suggesting that this phenomenon occurred both as there and elsewhere.

The takeaway from the story is that while they are usually thought of as pathogens, including particularly nasty wound infections like gangrene, bacteria can also be important for wound healing. Wound healing itself is a very complex process, involving not only the skin, but also the immune system and circulatory system, as the skin surface and underlying tissues repair themselves. To add another layer of complexity, the human skin surface is home to a vibrant microbiota, including bacteria, fungi and viruses that can help and hinder this delicate process.

The many functions of the skin microbiota

One of the important functions of the skin microbiota is to keep pathogens away from healing wounds, which also serve as major entry points for microorganisms. This can be achieved directly, through the production of antimicrobial molecules that kill potential threats, or indirectly when resident bacteria disrupt the disease-causing mechanisms of pathogens. Another indirect mechanism is that members of the skin microbiota put their host’s immune system on high alert.

A scanning electron microscope image of Staphylococcus epidermidis, a common skin commensal in humans.

A scanning electron microscope image of Staphylococcus epidermidis, a common skin commensal in humans.

Source: NIAID/Flickr

The skin microbiota can participate in and even initiate the cascade of immunological responses necessary to heal wounds. For example, members of the skin microbiota are important for initiating the first steps of healing. Commensal bacteria that enter the wounds cause the activation of immune cells known as neutrophils, which are important for activating rapid, innate immune responses. The neutrophils begin to express a chemical messenger called CXCL10, which in turn recruits more immune cells and kills other members of the microbiota in the wound to reduce the risk of infection.

One well-studied member of the skin microbiota is Staphylococcus epidermidis, which can promote wound healing in many ways. First, it can produce specific compounds, such as lipoteichoic acid, which limits inflammation and promotes a transition to the proliferative phase of wound healing, in which skin cells multiply and close the wound. Second, S. epidermis can also interact with the host’s adaptive immune system, encouraging immune cells called T cells to accelerate closure.

Bacteriotherapy to reduce biofilm-forming microbes

Bacterial skin infections affect hundreds of millions of people every year, raising the question: can our native skin microbiota be harnessed to treat these types of infections? Chronic wounds, such as ulcers, are often at high risk of infection due to their long healing time and therefore a longer period of vulnerability. A ‘bacteriotherapy’ approach with Lactobacillus plants has been tested in patients suffering from leg ulcers infected with multiple biofilm-forming bacteria. Although the study did not constitute a clinical trial, L. plants application to the wounds appeared to reduce the area of ​​the ulcers as well as the abundance of pathogens, including Staphylococcus aureus And Pseudomonas aeruginosathese are common biofilm-forming wound infections.

L. plants belongs to a group of bacteria known as lactic acid bacteria (LAB) that are often used in probiotic applications. Their frequent use is partly due to their non-pathogenicity, which provides safety for a variety of healthcare and nutritional science applications. L. plants cannot achieve its effects solely by directly antagonizing wound pathogens, such as P. aeruginosabut also through interaction with the immune system. L. plants The treatment appeared to promote the recruitment of neutrophils – those immune first responders – as well as fibroblasts and endothelial cells to the ulcer, which may have contributed to the improved granulation. However, the exact mechanisms, as well as an approved bacteriotherapy treatment, are still elusive.

Engineering bacteria to promote wound healing

There is ongoing cross-talk between the skin microbiota and the host immune system

There is ongoing cross-talk between the skin microbiota and the host immune system

Source: Swaney MH et al./Infection and Immunity, March 2021

In addition to bacteriotherapy approaches to treat wound infections, methods are also being explored to engineer bacteria to perform specific functions in wound environments. Due to rampant and ever-increasing resistance, we urgently need to move away from antibiotics as the primary therapeutic strategy for all types of bacterial infections, including those of the skin. One option is to engineer bacteria specifically designed to perform the beneficial functions of normal skin microbiota, such as modulation of the immune system.

An example of this technique in action comes from a recent study in which researchers developed a so-called bacterium Limosilactobacillus reuteri R2LC to produce the human immunochemical messenger CXCL12-α when introduced into a wound. They conducted a randomized, blinded, and placebo-controlled human study of the treatment, called ILP100-Topical. Reapplication of ILP100-Topical was not only well tolerated by subjects, but also helped to shorten healing time and increase the number of wounds healed after 19 days.

These types of studies are still scarce, which makes them even more special. “I am extremely proud that with this project we have achieved the first human study initiated in the laboratory by one of my PhD students,” says Professor Mia Phillipson from Uppsala University in Sweden. whose research group conducted the study. “This is the first study published testing this approach in humans to accelerate the healing of induced skin wounds,” she explained.

The skin: a new frontier?

The skin is the largest organ of the human body and the first defense barrier for everything inside against everything outside. The skin microbiota inhabits the surface of this barrier, where the inside may occasionally meet the outside, prompting battles for colonization and host protection. This delicate ecosystem clearly shows promise for treating wounds and other skin conditions, but much work remains to be done before wounds are healed by bacteria faster than you can say “Angel’s Glow.”

How can maggots be used to treat wounds and fight infections? What stands in the way of maggot therapy becoming mainstream? Tune in to ASM’s Mbiotic Minutes, a video series on trending topics in the microbial sciences, to find out.

source : www.miragenews.com

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