Antimicrobial Properties of Chitosan and Chitosan Derivatives in the Treatment of Enteric Infections

Abstract

Antibiotics played an important role in controlling the development of enteric infection. However, the emergence of antibiotic resistance and gut dysbiosis led to a growing interest in the use of natural antimicrobial agents as alternatives for therapy and disinfection. Chitosan is a nontoxic natural antimicrobial polymer and is approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration). Chitosan and chitosan derivatives can kill microbes by neutralizing negative charges on the microbial surface. Besides, chemical modifications give chitosan derivatives better water solubility and antimicrobial property. This review gives an overview of the preparation of chitosan, its derivatives, and the conjugates with other polymers and nanoparticles with better antimicrobial properties, explains the direct and indirect mechanisms of action of chitosan, and summarizes current treatment for enteric infections as well as the role of chitosan and chitosan derivatives in the antimicrobial agents in enteric infections. Finally, we suggested future directions for further research to improve the treatment of enteric infections and to develop more useful chitosan derivatives and conjugates.

Keywords: antibacterial; antifungal; antimicrobial; antimicrobial mechanisms of chitosan; chitosan; colonization resistance; drug delivery; enteric infection; gut microbiota.

Figure 1

Structure of chitosan.

Figure 2

Schematic diagram of chitosan chemical modification.

Figure 3

Teichoic acid polymers are located within Gram-positive cell wall.

Figure 4

Cell envelope of Gram-negative bacteria.

Figure 5

Schematic overview of fungal cell wall structure.

Figure 6

Schematic overview of action modes of chitosan on pathogen microorganisms. (A) Gram-positive bacteria, (B) Gram-negative bacteria, and (C) fungi. Owing to negative charges of WTAs in gram-positive bacteria, LPS in gram-negative bacteria, and phosphorylated mannose in fungi, positively charged chitosan are neutralized by above-mentioned components and induce leakage of intracellular components. Moreover, chitosan chelates metal cations on surface of bacteria, resulting in rupture of microbial cell membrane. High-molecular weight (MW) chitosan hinders exchange of nutrients by binding to porins on OM of Gram-negative bacteria, and thereby leading to bacterial cell death. Low-molecular weight (MW) chitosan can inhibit DNA/RNA or protein biosynthesis after penetrating into cytoplasm. Additionally, low-MW chitosan can induce mitochondrial dysfunction and reduced ATP production.

Figure 7

Immune response and colonization resistance.