How Chitosan Fights Infections

Chitosan is a natural, non-toxic antimicrobial polymer with GRAS (Generally Recognized as Safe) approval from the US FDA. It's nature's second most abundant polymer after cellulose, extracted from chitin found in fungal cell walls and crustacean shells.

Scientists create chitosan by modifying chitin, the original polymer, through deacetylation. This process gives chitosan its infection-fighting capabilities and enhances its bioactivity.

Chitosan’s Biological Properties:

• Biodegradable: Chitosan breaks down naturally in the body, making it safe for humans and the environment.
• Biocompatible: Unlike some foreign bodies, chitosan works well with human tissues, reducing the risks of immune rejection or adverse reactions.
• Non-toxic: Chitosan is safe for cells and tissues and is ideal for medical applications.
• Antimicrobial: Fights bacteria and fungi directly by breaking down their cell walls to prevent infections.
• Adsorption: Can bind to other molecules to help remove toxins, deliver drugs, and target bacteria.
• Antioxidant: Neutralize free radicals to reduce inflammation and support healing.
• Humectant: Retains moisture, creating a hydrated environment that promotes wound healing and skin health.
• Hemostasis: Stops bleeding fast as it binds with negatively charged blood cells to trigger platelet activation and blood clotting.

Chitosan consists of two key components distributed along its chain:

• D-glucosamine (the deacetylated unit).
• N-acetyl-D-glucosamine (the acetylated unit).

The balance between these alters chitosan's physical and biological properties:

• Degree of Deacetylation (DD): A higher DD means more D-glucosamine units with a positive charge. These free amino groups help chitosan bind better to negatively charged surfaces like bacterial cell walls and mucus.
• Molecular Weight (MW): MW is the polymer chain size. High-MW chitosan (>250 kDa) forms durable, dense films suitable for wound dressings and water filtration because it's less soluble. Low-MW chitosan (50–250 kDa) is more soluble and can easily penetrate cells.

Chitosan is a widely available polysaccharide with strong antifungal, antiviral, and antibacterial effects.

Chitosan prevents infections and stops the growth of harmful bacteria, fungi, and yeasts. Its unique molecular structure has a positive charge due to the free amino groups from D-glucosamine, which gives chitosan its bioactive properties.

This positive charge binds chitosan directly to negatively charged bacterial and fungal cell membranes. In bacteria, these negative charges come from molecules like lipopolysaccharides (LPS) in Gram-negative bacteria and teichoic acids in Gram-positive bacteria. In fungi and yeasts, negative charges are present on cell wall components like glucans and mannans.

When bound, chitosan disrupts the membrane's structure by increasing its permeability and causing cell leakage. By breaking down these protective barriers, chitosan effectively kills the pathogens. It can even insert itself into the membrane's lipid layers, forming pores that worsen the leakage.

Research by Chung et al. demonstrated how chitosan disrupts the cell structures of both Escherichia coli and Staphylococcus aureus by binding to their enzymes and nucleotides.

Because of these strong antibacterial properties, chitosan has found its way into commercial disinfectants. Compared to other disinfectants, it provides higher antibacterial activity, works against a broader range of microbes, and is less toxic to human cells, making it a safer choice (Liu et al., 2001).

Chitosan can enter the bacterial cell and latch onto its DNA, inhibiting RNA synthesis and protein production and killing the cell. Its positive charge binds tightly to these nucleic acids' negatively charged phosphate groups.

This disrupts transcription (DNA to mRNA) and translation (mRNA to proteins), halting the cell's ability to make essential proteins. Chitosan also inhibits fungal growth by disrupting ATP synthesis, which deprives cells of energy.

Chitosan's effectiveness varies by molecular weight (MW) measured in kDa:

• Low MW Chitosan (50–250 kDa): Penetrates cells more efficiently, directly disrupting RNA synthesis and damaging cell membranes from within.
• High MW Chitosan (>250 kDa): stays on the bacterial surface, creating a barrier to block nutrient and gas exchange.
• Oligo-Chitosan (<50 kDa): Small and highly mobile oligo-chitosan can quickly interfere with transcription and translation, making it effective against bacterial growth at a molecular level.

By tailoring MW, chitosan can be customized for specific applications like wound dressings, agricultural treatments, or targeted drug delivery, making it a versatile tool against pathogens.

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Chitosan acts as a chelating agent, disrupting bacterial growth and function by attaching to metal ions on cell surfaces.

Metabolic Pathways Disruption

Chitosan's positive charge enables it to bind effectively with ions, including:

• Calcium (Ca²⁺)
• Magnesium (Mg²⁺)
• Iron (Fe²⁺)
• Zinc (Zn²⁺)

These ions maintain cell stability and support metabolic functions. When chitosan captures them, it interferes with cellular processes that depend on these ions, leading to cell stress and dysfunction.

Stronger Chelation at Higher pH

At higher pH levels (7 – 8.5), chitosan's amino groups partially deprotonate, shifting the binding from simple electrostatic attraction to stable metal complexes that disrupt cellular function.

Membrane Destabilization

Chelation disrupts the cell's surface balance, causing phosphate groups on the membrane to repel each other. This destabilizes the membrane structure until it ruptures.

Blocking Toxin Production

Bacteria require calcium and magnesium to make toxins. Chitosan's ability to bind with these metal ions inhibits cell growth, reducing toxin synthesis and overall pathogenicity. This dual action makes chitosan a powerful agent against bacteria, destroying cells and preventing the release of harmful toxins.

Chitosan works as a blocking agent that hinders bacterial growth by forming a dense barrier around microbial cells. This barrier works by:

• Preventing nutrient intake by blocking porins, which act as pores on the microbial cell surface.
• Restricting oxygen access by cutting off gas exchange.

This effect is powerful against aerobic (oxygen-dependent) bacteria. Without oxygen and nutrients, these bacteria can't grow and eventually die.

One notable example is when bacteria produce bacterial cellulose (BC) on surfaces where air meets liquid. Chitosan forms a barrier that restricts oxygen flow reaching them, causing hypoxic cell death. This unique action makes chitosan highly effective in controlling bacterial growth in oxygen-rich environments.

As a natural biopolymer, chitosan integrates seamlessly with human tissue, triggering minimal risk of immune or inflammatory responses. Its molecular structure closely resembles glycosaminoglycans, polysaccharides naturally occurring in body tissues, allowing it to blend fully within biological systems. This biocompatibility is especially important in medical devices like sutures, where infection control and tissue integration are crucial.

Chitosan supports a balanced healing process. It modulates immune responses by:

• Promoting macrophage activity (cells that clear harmful particles).
• Stimulating fibroblast activity (cells involved in tissue repair).
• Avoiding excessive inflammatory reactions.

Its biocompatibility comes from key qualities: bioadhesive, bioactive, biodegradable, and non-toxic, making it safe and effective for medical applications.

Therapeutical Uses:

• Surgical Sutures: Absorbable sutures naturally bond with tissue and reduce infection risk.
• Wound Dressings: Its antimicrobial properties help prevent infection while promoting healing.
• Hydrogels: Chitosan-based hydrogels maintain wound hydration, support healing, and reduce scarring.
• Drug Delivery Systems: Chitosan can carry and release medications gradually, making it valuable for targeted treatments.
  

Coating fibers with chitosan increases cell growth and creates a strong antibacterial barrier, making it a promising strategy for next-generation sutures and wound dressings. It is approved for dietary applications in Japan, Italy, and Finland.

Unlike synthetic polymers, the body can naturally break down chitosan through enzymes like lysozyme in human tissues and lipase in saliva and digestive fluids. Chitosan sutures don't need to be removed as they dissolve over time, reducing secondary infection risk and patient discomfort.

Chitosan's biodegradation rate can be tailored for specific needs. Low molecular weight (MW) and degree of deacetylation (DD) speed up breakdown, ideal for rapid absorption, while higher MW and DD slow degradation for longer-lasting applications.

The byproducts are all non-toxic, eliminating concerns of harmful accumulation in the body. Chitosan's environmental sustainability is another plus, as it leaves no harmful residues.

Chitosan demonstrates broad-spectrum antimicrobial activity, effectively targeting multiple types of disease-causing organisms:

Gram-positive Bacteria

Chitosan membrane-disrupting properties are particularly effective against bacteria with a simple cell wall:

• Staphylococcus aureus (causing skin infections)
• Streptococcus (causing strep throat).

In gram-positive bacteria, chitosan's positive charge binds electrostatically to the negatively charged teichoic acids in the thick peptidoglycan layer of the cell wall. This binding destabilizes the cell wall structure, blocking ion passage and weakening membrane integrity. Studies confirm that chitosan's disruption of the cell wall leads to leakage of proteins and other essential intracellular components, allowing chitosan to penetrate further into the cell.

In gram-positive bacteria, metal ions stabilize the cell wall by binding to wall teichoic acids (WTAs), reducing repulsion among negatively charged phosphate groups and maintaining osmotic balance. By chelating these ions, chitosan further weakens the cell wall structure, adding another layer of antimicrobial action.

This multi-step disruption of cell wall integrity highlights chitosan's strong potential as an antimicrobial agent, particularly against gram-positive bacterial infections.

Gram-negative Bacteria

An extra outer membrane protects gram-negative bacteria:

• Escherichia coli (causing food poisoning)
• Pseudomonas aeruginosa (causing wound infections)

This outer membrane, made up of lipopolysaccharides (LPS), carries a high negative charge that strengthens the bacterial defense.

Chitosan counters this protection through its positive charge, which interacts with the negatively charged LPS, disrupting the outer membrane and increasing permeability. Once through the outer membrane, chitosan reaches the inner membrane, where it blocks nutrient flow, causes leakage of cytosolic contents, and leads to cell death.

This dual action targeting the outer and inner membranes highlights chitosan's potential as an antimicrobial agent against difficult-to-treat bacterial infections. Despite the differences between gram-positive and gram-negative bacteria, research supports chitosan's ability to destroy both types, supporting its diverse applications in infection control.

Fungi

Fungi include yeasts, molds, mildews, rusts, and mushrooms. Chitosan has proven antifungal properties, making it effective against fungal pathogens like Candida and Aspergillus that impact plants and animals.

How Chitosan Fights Fungi

Chitosan disrupts fungal cells by breaking down the cell membrane, causing leakage of cell contents. In some cases, chitosan can even enter fungal cells, interfering with DNA and RNA synthesis, protein production, and mitochondrial function, effectively blocking growth and reproduction.

Chitosan attacks fungal cells on multiple fronts:

• Cell Membrane Disruption: It destabilizes the fungal cell membrane, causing leakage of vital components.
• Intracellular Interference: Low MW chitosan can penetrate the cell wall and reach the cytoplasm to disrupt DNA, RNA, and protein synthesis and halt cellular functions.
• Mitochondrial Disruption: Chitosan interferes with mitochondrial function, reducing energy production and further inhibiting growth.
  

Factors Influencing Efficacy

Chitosan's antifungal activity varies based on its MW, DD, and environmental pH:

• Low MW Chitosan: Enters cells more effectively, targeting intracellular processes.
• High MW Chitosan: Forms surface barriers, preventing cell membrane exchange.
• High DD and Low MW: Boost fungicidal activity, especially in low pH environments.

Chitosan's remarkable adaptability positions it as a powerful agent for innovative applications in medicine and agriculture.

Viruses

Chitosan can help prevent viruses from entering host cells by interfering with their viral attachment process. Beyond its direct and critical effect, chitosan has mild immunostimulatory effects, which help activate the body's immune response to viruses.

Researchers are also exploring chitosan-based nanoparticles as carriers for antiviral drugs. These nanoparticles could potentially increase the precision and effectiveness of antiviral treatments, allowing for better targeting of infected cells and reduced side effects.

Several intrinsic and extrinsic factors influence chitosan, including:

• Molecular Weight (MW): Lower MW reduces viscosity and improves solubility. It can inhibit mRNA synthesis and interact with cellular membranes, disrupting their permeability and ultimately leading to cell death. Higher MW improves durability and film-forming ability, forming a protective barrier. It can completely cover the membrane surface, preventing the exchange of nutrients and gases, resulting in cell death.
• Degree of Deacetylation (DD): Higher DD means a stronger positive charge, enhancing antimicrobial action.
• Solubility: Impacts how well chitosan dissolves in different environments. Increased solubility is helpful for liquid applications like sprays, while less soluble forms are effective as solid coatings.
• pH Level: Chitosan's antimicrobial activity is highest in acidic conditions (below pH 6.5) due to its low solubility.
• Temperature: Influences chitosan's stability and activity over time. Chitosan stored at 4 °C for 15 weeks showed stronger antimicrobial activity than when stored at 25 °C.
• Concentration: Chitosan's antimicrobial action varies by concentration. At low concentrations, it disrupts cell membrane fluidity by binding to negatively charged microbial surfaces, leading to cell death.High concentrationsform a coating that blocks nutrient and gas exchange, ultimately killing the cell and preventing aggregation.
• Targeted Microorganism: Different microbes, such as gram-positive and gram-negative bacteria, respond uniquely to chitosan. Customizing properties like MW and DD allows chitosan to target specific pathogens more effectively.

Chitosan's DD and MW can be customized for different applications based on the desired strength, solubility, and biological activity.

Chitosan's wide availability due to abundant sources, versatility, low cost, and unique and safe properties allow it to be used in many fields beyond treating infectious diseases. For example, chitosan has been widely used in these scientific fields for many years:

• Agriculture.
• Aquaculture.
• Tissue Engineering.
• Wastewater Treatment.
• Cosmetics.
• Supplements.

Our Industry Applications

As infectious diseases and drug-resistant pathogens continue challenging global health, chitosan emerges as a powerful alternative. Its natural antimicrobial properties disrupt bacteria, fungi, and viruses, while its biocompatibility and adaptability make it a safe and versatile solution for diverse applications.

Chitosan's customizable molecular structure—with adjustable molecular weight and degree of deacetylation—enables precise tailoring for specific pathogens and settings. With mounting antimicrobial resistance, chitosan is a powerful, adaptable, and sustainable agent, offering broad potential to transform infection control and prevention across medical and environmental fields.