Lactobacillus johnsonii genome decoded

Source: Proceedings of the National Academy of Sciences 101, 2512-2517

The human gastrointestinal tract (MDT) is a nutrient-rich environment colonized by a large and complex collection of microorganisms. The microorganisms play an important role in the function and development of the intestine. The composition of the microflora varies individually, depending on age and from intestinal section to intestinal section. It contains more than 500 types of bacteria. The bacteria are involved in the digestion of polysaccharides and proteins and are responsible for a large part of MDT metabolism. They also produce vitamins, short-chain fatty acids, and other nutrients for their host.

A balanced and diverse microflora is essential for healthy intestinal function and defense against enteric pathogens. Therefore, several Lactobacillus species, some bifidobacteria, and foods fermented by them are widely marketed as probiotic foods. The Lactobacillus-Enterococcus group accounts for 6% of the composition of the faecal microflora and 23% of the caecal microflora at the junction of the small and large intestine. Of the more than 50 known Lactobacillus species, the 'acidophilus complex', which consists of 6 closely related species, received particular attention because probiotic properties are ascribed to these microorganisms and they are regularly isolated from human stool and mucous membranes.

L. johnsonii NCC533 (formerly L. acidophilus La1) has been intensively investigated in recent years with regard to its probiotic activities (immunomodulation, inhibition of pathogens, attachment to epithelial cells). The genome of this bacterium has now been completely sequenced by a research group from Switzerland (Nestlé Research Center) and the USA (North Carolina State University, Raleigh and University of Georgia, Athens).

The genome is 1.992.676 base pairs long. The absence of genes for the synthesis of amino acids, purine nucleotides and most of the cofactors (thiamine, nicotinic acid, riboflavin, biotin, cobalamin, pantothenic acid, pydridoxine) is striking. To balance this, a remarkable number of unusual and often duplicated amino acid permeases, peptidases and phosphotransferase-type transporters are found, suggesting a strong dependence of L. johnsonii NCC533 on its host or other gut organisms. The genome sequence also predicts 12 large and unusual surface proteins that may be important for attachment to gut epithelial cells.

Three bile salt hydrolases (BSHs) and two bile acid transporters thought to be important for survival in MDT were also detected. BSHs are thought to facilitate the incorporation of cholesterol or bile into the bacterial membrane, altering the fluidity or charge in a way that affects sensitivity to α-defensins and other host defense molecules. Genes for the de novo synthesis of the pyrimidines dTMP, UMP and CMP are present, but not for purine biosynthesis. There are genes for the conversion of inosine, xanthine and hypoxanthine into IMP, GMP and AMP. L. johnsonii NCC533 is thus auxotrophic for many building blocks, consistent with its demanding nutritional requirements. The complete dependence on exogenous amino acids is accompanied by an unusually large number and variety of proteinases, peptide transporters and peptidases (> 25 cytoplasmic peptidases).

Overall, L. johnsonii NCC533 seems to be better adapted to the milieu of the upper MDT compared to Bifidobacteria, Bacteroides and other colonic bacteria. However, it remains to be clarified whether L. johnsonii is an “obligate” commensal of the MDT or whether it has other reservoirs. The genome of L. johnsonii is largely identical to that of its closest relative, L. gasseri. Basic metabolism genes show >94% sequence identity. The complete genome sequence provides the basis for a better understanding of commensal interactions with the 'human' host.

Source: Kulmbach [KRÖCKEL]

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