Lactobacillus reuteri mucus-binding protein (MUB) is a cellsurface protein that is involved in bacterial interaction with mucus and colonization of the digestive tract. The 353-kDa mature protein is representative of a broadly important class of adhesins that have remained relatively poorly characterized due to their large size and highly modular nature. MUB contains two different types of repeats (Mub1 and Mub2) present in six and eight copies, respectively, and shown to be responsible for the adherence to intestinal mucus. Here we report the 1.8-Å resolution crystal structure of a type 2 Mub repeat (184 amino acids) comprising two structurally related domains resembling the functional repeat found in a family of immunoglobulin (Ig)-binding proteins. The N-terminal domain bears striking structural similarity to the repeat unit of Protein L (PpL) from Peptostreptococcus magnus, suggesting binding in a non-immune Fab-dependent manner. A distorted PpL-like fold is also seen in the C-terminal domain. As with PpL, Mub repeats were able to interact in vitro with a large repertoire of mammalian Igs, including secretory IgA. This hitherto undetected activity is consistent with the current model that antibody responses against commensal flora are of broad specificity and low affinity.
The human gastrointestinal tract (GIT)3 contains trillions of bacteria, representing hundreds of species and thousands of subspecies (1). They outnumber our own cells by a factor of 10 and contribute many physiological capabilities, including the provision of metabolic attributes not encoded in the human genome (2). A protective layer of mucus, consisting of a complex mixture of large, highly glycosylated proteins (mucins) (3), covers the epithelial cells of the intestine and offers an attachment site for the colonizing bacteria. These bacteria play important roles in maintaining normal gut function and in building resistance of the host to pathogenic micro-organisms (4, 5). Some may use mucins as their major carbon and energy source (6, 7).Lactobacilli are Gram-positive microaerophilic bacteria naturally present in the dominant colonic microbiota and have been considered to be beneficial for human health (8). They are commonly used as probiotics, which are defined by the Food and Agriculture Organization/World Health Organization as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (9). As probiotic agents, lactobacilli can prevent or alleviate infectious diarrhea through their effects on the immune system and promote host resistance to colonization by pathogens (10, 11), and many have been shown to adhere to intestinal mucus (12-19). Confirmation of this lactobacillus-mucus association has not only been observed in vitro, but has also been validated by ex vivo/in vivo microscopic analysis of biopsy samples (20,21). In most cases, lactobacilli adhesion to mucus has been proposed to be mediated by proteins (22-30). Compared with the present understanding of the adhesive mechanisms of human...