Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection

Abstract

Mucus layers often provide a unique and multi-functional hydrogel interface between the epithelial cells of organisms and their external environment. Mucus has exceptional properties including elasticity, changeable rheology and an ability to self-repair by re-annealing, and is therefore an ideal medium for trapping and immobilising pathogens and serving as a barrier to microbial infection. The ability to produce a functional surface mucosa was an important evolutionary step, which evolved first in the Cnidaria, which includes corals, and the Ctenophora. This allowed the exclusion of non-commensal microbes and the subsequent development of the mucus-lined digestive cavity seen in higher metazoans. The fundamental architecture of the constituent glycoprotein mucins is also evolutionarily conserved. Although an understanding of the biochemical interactions between bacteria and the mucus layer are important to the goal of developing new antimicrobial strategies, they remain relatively poorly understood. This review summarises the physicochemical properties and evolutionary importance of mucus, which make it so successful in the prevention of bacterial infection. In addition, the strategies developed by bacteria to counteract the mucus layer are also explored.

Fig. 1

Similarity in the amino acid sequence between qniumucin from jellyfish and human MUC5AC. A similar tandem repeat of eight residues is found in both mucins and the boxes highlight four of these similarities. Although the human mucin is more flexible, both proteins form a gel in water. Reprinted (adapted) with permission from (Masuda et al. Mucin (qniumucin), a glycoprotein from jellyfish, and determination of its main chain structure. J. Nat. Prod. 70, 1089–1092 (2007). Copyright (2007) American Chemical Society

Fig. 2

Similarity between (a) mucus secretory cells of Cnidarians (b) human airway epithelium. Coral mucocytes and human goblet cells are structurally similar and perform similar roles, which can be seen in the histological images of (c) a section from the coral Coelastrea aspera, stained with toluidine blue, showing coral mucocytes surrounded by ectodermal cells (scale bar 10 µm) and (d) a section of human trachea, H & E staining, showing human goblet cells surrounded by ciliated epithelial cells (scale bar 20 µm)

Fig. 3

The properties of mucus, which allow resistance to microbial colonisation, can be divided into physical and chemical processes. Physical processes include its gel properties, such as thickness, entrainment, sloughing and viscosity. Chemical processes include those conferred by enzymes and secondary metabolites. The antibacterial metabolite shown here, Eunicellol A, is secreted into the mucus of the Arctic soft coral Gersemia fruticosa

Fig. 4

Mucinases are important hydrolytic enzymes that can contribute to the penetration of mucus, an important mechanism of bacterial pathogenesis. E. coli degrades mucins using a zinc metalloprotease and members of the genus Vibrio produce a hemagglutinin protease. Using these mucolytic enzymes, pathogens can cross human and coral protective mucus layers. Image adapted from.