A Microbial Biorealm page on the genus Lactobacillus johnsonii
Higher order taxa
Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae; Lactobacillus
Description and significance
Lactobacillus johnsonii is one of the many microorganisms that reside in the human intestine. Like all species of the Lactobacillus genus, it is an anaerobic, Gram-positive bacterium, which has a rod-like shape and does not undergo spore formation (1). The human gastrointestinal tract in which L. johnsonii resides is abundant with nutrients and relies upon more than 500 microbial species that inhabit it in order to develop and function properly. Specifically L. johnsonii and other GI tract microbes aid in polysaccharide and protein digestion and also generate a variety of nutrients, including vitamins and short-chain fatty acids that make up 15% of a human’s total caloric intake. In addition, because L. johnsonii is able to undergo fermentation and can therefore make lactic acid, it plays a major role in the fermentation and preservation of various food items, such as dairy, meat, vegetable products, and cereal (1, 2). Finally, L. johnsonii is characterized as being part of the “acidophilus complex” of the Lactobacillus genus. This complex is comprised of six Lactobacillus species that are thought to be involved in probiotic activities, meaning they are able to undergo processes that are thought to be beneficial to human general health and well-being (2, 3). Such probiotic benefits particularly attributed to L. johnsonii include immunomodulation, pathogen inhibition, and epithelial cell attachment (2).
The genome of L. johnsonii strain NCC 533 was sequenced by the Nestle Research Center in Switzerland through the method of shotgun sequencing. The 1,992,676 base pair genome has a circular topology and is composed of 1,821 protein coding genes with 79 tRNAs (2, 4, 14). The Lactobacillus genus as a whole is characterized by its low Guanine+Cytosine content. L. johnsonii, in particular, contains a G+C content of 34.6% (2). Interestingly, L. johnsonii contains no genes which encode for the biosynthetic pathways necessary to generate amino acids and necessary cofactors. Rather, the genome contains of many amino acid proteases, peptidases, and phosphotransferase transporters and hence requires amino acids and peptides that come from its environment. In addition, genome sequencing has revealed that L. johnsonii contains all of the genes necessary for the synthesis of pyrimidines, but lacks genes necessary for the synthesis of purines. Thus, L. johnsonii also must depend on its environment in order to acquire purine nucleotides. Since this organism must obtain amino acids and purine nucleotides from exogenous sources, it is thought that it relies on its human host or other intestinal microorganisms in order to obtain such monomeric nutrients (2).
Cell structure and metabolism
The cell surface of L. johnsonii contains various types of cell-surface proteins which are important in helping the microorganism attach to the mucosal surfaces of the GI tract. In addition, these cell-surface proteins can play a role in stimulating immune cells and can thus be one of the mechanistic explanations underlying the probiotic property of immunomodulation often attributed to L. johnsonii. Examples of these cell-surface proteins include mucus-binding proteins, glycosylated fimbriae, and an IgA protease (2).
As an anaerobic, lactic acid producing bacterium, L. johnsonii obtains its energy by fermenting disaccharides and hexoses to lactic acid. Specifically, the sugars it uses as substrates include galactose, maltose, sorbose/sorbitol, gentiobiose, isoprimerevose, isomaltose, and panose (2). L. johnsonii’s ability to undergo fermentation and thus produce lactic acid makes it a widely used microorganism in the industrial fermentation of dairy, meat, and vegetable products (3). However, as mentioned above, L. johnsonii lacks the biosynthetic pathways necessary for the generation of essential nutrients such as amino acids, purine nucleotides, and cofactors. Because of this, the genes which code for transporters in this microorganism are highly expressed and thus L. johnsonii contains a great number of certain transporters that are less frequent in other microorganisms. Specifically, it contains an abundance of AA-permease transporters and phosphotransferase (PTS)-type transporters. In addition, L. johnsonii has numerous various proteinases, peptide transporters and peptidases in order to acquire nutrients from exogenous sources (2).
Due to its metabolic limitations and reliance on exogenous sources of nutrients, L. johnsonii is typically found in human and animal gastrointestinal tract where it can obtain nutrients from its host. As an auxotrophic bacterium that lacks certain enzymes needed for the digestion of complex carbohydrates, it is unable to compete with other GI tract bacteria such as Bifidobacteria, which inhabit the colon. Therefore L. johnsonii resides in the upper GI tract, which is rich in amino acids and peptides. Specifically, it is one of the dominant microorganisms found at the junction between the ileum of the small intestine and the cecum of the colon (2). Other species within the Lactobacillus genus can be found in food, vegetation, sewage, and various areas of the human body. In humans, Lactobacillus species can be found in the intestine, oral cavity, and the vagina (1). L. johnsonii, in particular, has many genes and transporters that allow it to release bile salt hydrolase, an important enzyme that is characteristic of microorganisms that live in the GI tract. Since L. johnsonii devotes many genes for the encoding of bile salt hydrolase, its importance and ability to compete and survive in its ecosystem can be correlated with its ability to produce such large amounts of this essential enzyme.
In addition, lactic acid bacteria, such as L. johnsonii are able to produce bacteriocins which have antibacterial properties that lactic acid bacteria can use against other microorganisms, thus providing them with ways to survive in their ecosystem. For example, L. johnsonii is able to produce Lactacin F, a bacteriocin which can kill other Lactobacillus species as well as Enterococcus species in the GI tract. Thus, this microbe is thought to use this bacteriocin as a way to compete in the microbe-rich environment in which it lives (2, 5). Some lactic acid bacteria have been shown to use quorum sensing as a regulator for the expression of genes involved in the production of bacteriocins. For example, some species of the Lactobacillus genus such as Lactobacillus sake have been shown to utilize quorum sensing as a means of regulating bacteriocin gene expression (6).
L. johnsonii is not known to be pathogenic to humans. On the contrary, it is shown to be a beneficial microorganism which resides in the human intestine and is characterized by various probiotic properties (1, 2, 3). Other species in the Lactobacillus genus are also known to be non-pathogenic. There have, however, been a small number of incidents where Lactobacillus has been a pathogen, but these few cases have involved people with previous diseases (1).
Application to Biotechnology
Lactobacillus johnsonii is able to undergo fermentation and produce lactic acid. This biochemical compound produced by L. johnsonii and other lactic acid bacteria provides the sour taste and texture along with a preservative effect for many consumed foods, especially milk and dairy products. For this reason, Lactobacillus and other lactic acid bacteria are commonly used in the industrial production of dairy products where they can be used as starter cultures necessary to generate products such as yogurt. They can also be introduced into food products for their probiotic effects (3). For example, the presence of L. johnsonii in milk can help thicken mucous membranes and reduce the risk of developing stomach ulcers caused by Helicobacter pylori (11). The effect of Lactobacillus on H. pylori has shown to have greater effect when the Lactobacillus species is present in a cultured form such as milk (12). Thus, such results indicate the possible further incorporation of the Lactobacillus species and other lactic acid bacteria in the industrial production of dairy products for their beneficial use as prophylaxis.
In addition, a study conducted by La Ragione et al. (2004) addressed the beneficial use of L. johnsonii in the poultry industry. This study found that the administration of L. johnsonii in chickens helped control diseases caused by Escherichia coli and Clostridium perfringens. Thus, L. johnsonii has the potential to be directly used in the poultry industry as an alternative to antimicrobials (10).
As a probiotic bacterium with many potential benefits for human health, Lactobacillus johnsonii has recently been the subject of various research investigations, many of which show the potential of L. johnsonii as a treatment option for various human diseases. For example, one study by Kaburagi et al (2007) examined the effect of ingested Lactobacillus johnsonii in the diet of aged mice with Protein-Energy Malnutrition (PEM). PEM is an immune deficiency commonly seen in the human elderly population due to nutritional problems. In experiments done on aged mice through experiment-induced protein-energy malnutrition, the researchers were able to identify several immune system benefits associated with the inclusion of L. johnsonii La1 in the diet. Specifically, L. johnsonii was able to positively influence both the intestinal and systemic immune system by partially restoring the number of serum IgA, IgG, and CD8+ cells, and enhancing the formation of splenocytes; all of which had decreased as a result of a low protein diet leading to PEM (7).
Another study by Inoue et al (2007) investigated the influence of L. johnsonii on immune system responses associated with Atopic Dermatitis, an inflammatory dermatological disease. In a comparison of the expression of genes involved in Atopic Dermatitis, the investigators found that while a control group of mice showed increased cytokine and CD86 levels following induction of a skin lesion, mice which had been orally administered L. johnsonii showed no elevation in cytokine or CD86 levels (8).
Furthermore, L. johnsonii may even have a potential treatment role in the management of diabetes. One study by Yamano et al (2006) found that the oral administration of L. johnsonii reduced glucose and glucagon levels in diabetic rats which had been subject to intracranial injection of 2-deoxy-D-glucose (2DG). The investigators also present a possible mechanism by which L. johnsonii affects the autonomic nervous system and thus modulates an anti-diabetic response (9).
1. Falsen, E., Pascual C., Sjoden B., Ohlen M., and Collins M.D. “Phenotypic and phylogenetic characterization of a novel Lactobacillus species from human sources: description of Lactobacillus iners sp. nov.” International Journal of Systemic Bacteriology. 1999. Volume 49. p. 217-221.
2. Pridmore, R.D., Berger, B., Desiere, F., Vilanova, D., Barretto, C., Pittet, A.C., Zwahlen, M.C., Rouvet, M., Altermann, E., Barrangou, R., Mollet, B., Mercenier, A., Klaenhammer, T., Arigoni, F., and Schell, M.A. “The genome sequence of the probiotic intestinal bacterium Lactobacillus johnsonii NCC 533.” Proceedings of the National Academy of Sciences of the United States of America. 2004. Volume 101. p. 2512-2517.
3. Klaenhammer, T.R., Azcarate-Peril, M.A., Altermann, E., and Barrangou, R. “Influence of the Dairy Environment on Gene Expression and Substrate Utilization in Lactic Acid Bacteria.” The Journal of Nutrition. 2007. Volume 137. p. 748S-750S.
4. Comprehensive Microbial Resource. Lactobacillus johnsonii NCC 533 Genome Page.
5. Abee, T., Klaenhammer, T.R., and Letellier, L. “Kinetic Studies of the Action of Lactacin F, a Bacteriocin Produced by Lactobacillus johnsonii That Forms Poration Complexes in the Cytoplasmic Membrane.” Applied and Environmental Microbiology. 1994. Volume 60. p. 1006-1013.
6. Risoen, P.A., Brurberg, M.B., Eijsink, V.G., and Nes, I.F. “Functional analysis of promoters involved in quorum sensing-based regulation of bacteriocin production in Lactobacillus.” Molecular Microbiology. 2000. Volume 37. p. 619-628.
7. Kaburagi, T., Yamano, T., Fukushima Y., Yoshima, H., Mito, N., and Sato, K. “Effect of Lactobacillus johnsonii La1 on immune function and serum albumin in aged and malnourished aged mice.” Nutrition. 2007. Volume 23. p. 342-350.
8. Inoue, R., Otsuka M., Nishio, A., and Ushida, K. “Primary administration of Lactobacillus johnsonii in weaning period suppresses the elevation of proinflammatory cytokines and CD86 gene expressions is skin lesions in NC/Nga mice.” FEMS Immunology & Medical Microbiology. 2007. Volume 50. p. 67-76.
9. Yamano, T., Tanida, M., Niijima, A., Maeda K., Okumura, N., Fukushima, Y., and Nagai, K. “Effects of the probiotic strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats.” Life Science. 2006. Volume 79. p. 1963-1967.
10. La Ragione, R.M., Narbad, A., Gasson M.J., Woodward M.J. “In vivo characterization of Lactobacillus johnsonii FI9785 for use as a defined competitive agent against bacterial pathogens in poultry.” Letters in Applied Microbiology. 2004. Volume 38. p. 197-205.
11. Pantoflickova, D., Corthesy-Theulaz, I., Dorta, G., Stolte, M., Isler, P., Rochat, F., Enslen, M., Blum, A.L. “Favourable effect of regular intake of fermented milk containing Lactobacillus johnsonii on Helicobacter pylori associated gastritis.” Alimentary Pharmacology & Therapeutics. 2003. Volume 18. p. 805-813.
12. Hamilton-Miller, J.M. “The role of probiotics in the treatment and prevention of Helicobacter pylori infection.” International Journal of Antimicrobial Agents. 2003. Volume 22. p. 360-366.
13. National Center for Biotechnology Information (NCBI) Taxonomy Browser. Taxonomy ID: 33959.
14. National Center for Biotechnology Information (NCBI) Genome. Lactobacillus johnsonii NCC 533, complete genome.
Edited by Richard Sawaya, student of Rachel Larsen and Kit Pogliano