- 1 1. Classification
- 2 2. Description and significance
- 3 3. Genome structure
- 4 4. Cell structure
- 5 5. Metabolic processes
- 6 6. Ecology
- 7 7. Pathology
- 8 8. Current Research
- 9 9. References
a. Higher order taxa
Lactobacillus salivarius belongs to the terrabacteria group in the class Firmicutes. It is in the class Bacilli, of the order Lactobacillales, and belongs to the family Lactobacillus (“European Bioinformatics” 2018).
2. Description and significance
Lactobacillus salivarius is a well characterized, rod-shaped, Gram-positive species of probiotic bacteria (Chapot-Chartier et al. 2014). It is commonly isolated from human, porcine, and avian gastrointestinal tracts. L. salivarius is a lactic acid bacterium that has antimicrobial activity due to the production of bacteriocins, which directly inhibit pathogens (Messaoudi et al. 2013). Modern discoveries have demonstrated the effectiveness of the bacteriocins of L. salivarius against specific pathogens such as those that are responsible for foodborne illness, acne and other skin conditions, and irritable bowel syndrome in humans (Messaoudi et al. 2013, Corr et al. 2007, Deidda et al. 2018, Peran et al. 2005). L. salivarius has also been proven to fight the pathogen Staphylococcus aureus; L. salivarius can target both planktonic cells as well as biofilms of S. aureus through the secretion of anti-Staphylococcus proteins. (Kang et al. 2017) The bacteriocin properties of L. salivarius also are effective in food preservation (Messaoudi et al. 2013). New knowledge regarding the beneficial antibacterial properties of L. salivarius have led to an increase in the use of the strain as a replacement to previous topical and oral antibiotics (Corr et al. 2007). Further exploration of the mechanisms of L. salivarius’ probiotic and antimicrobial properties has the potential to yield new discoveries beneficial to human health.
3. Genome structure
The genome of L. salivarius is a circular chromosome of approximately 2,028,405 base pairs with a 32.7% G/C content (Ayala et al. 2017). Of all of the chromosomal genes, the function of 71% of these genes are known (Claesson et al. 2006). There are 1,982 protein coding sequences along with 64 tRNA and 31 rRNA sequences (Ayala et al. 2017). Additionally, this bacterial genome has a tetracycline resistance gene (Ayala et al. 2017). Of the entire genome of L. salivarius, 20% consists of four plasmids, two of which are megaplasmids (Raftis et al. 2014, Seol et al. 2011). Evidence shows these megaplasmids may be a possible mechanism used by the bacterium to expand and/or contract its genome to adjust to varying environmental conditions (Claesson et al. 2006). One of the megaplasmids identified encodes proteins involved in metabolic processes and expresses characteristics that can help L. salivarius survive within the gastrointestinal tract of humans (Claesson et al. 2006). However, the function of only 50% of the genes of the megaplasmid are known (Claesson et al. 2006).
4. Cell structure
L. salivarius bacteria are rod-shaped cells (bacilli). Along with all lactic acid bacteria, L. salivarius are Gram-positive due to the structure of their cell wall (Chapot-Chartier et al. 2014). The specific amino acid sequence of the peptide chains of the peptidoglycan layer impacts the bacteria’s interaction with host cells (Chapot-Chartier et al. 2014). One particular amino acid chain of the peptidoglycan in L. salivarius Ls33, for instance, is associated with the strain’s anti-inflammatory properties in intestinal cells (Macho et al. 2011). The cell wall also contains lipoteichoic acids (LTAs) and wall teichoic acids (WTAs) which are anionic molecules that play various functional roles in the cell. LTAs and WTAs can help establish a pH gradient across the cell wall, maintain cell shape, and recognize bacteriophages (Chapot-Chartier et al. 2014). The final component of the cell wall, the S layer, has been found to play a crucial role in the adhesion process of L. salivarius (Wang et al. 2017). Choline binding protein A (CbpA), an S-protein in the cell wall of L. salivarius REN, can recognize CbpA receptors on human intestinal host cell to facilitate the binding process. This adhesion allows the bacteria to exhibit its probiotic functions by protecting the epithelial lining of the gut and excluding pathogens (Wang et al. 2017).
5. Metabolic processes
L. salivarius is characterized as a lactic acid bacterium (LAB), which denotes its ability to produce lactic acid by fermentation (Kuratsu et al. 2010). Specifically, L. salivarius is a homofermentative bacterium, meaning it can only utilize carbohydrates to ferment sugars via the Embden-Meyerhof-Parnas (EMP) pathway. The sugars it can ferment include the monosaccharides glucose, ribose adonitol, galactose, fructose, mannose, mannitol sorbitol and N-acetylglucosamine, in addition to the disaccharides maltose, lactose, sucrose and trehalose (Claesson et al. 2006). Each of these sugars are commonly found in or produced from human dietary components, which is why L. salivarius thrives in the human gastrointestinal system (Claesson et al. 2006). L. salivarius is a facultative-anaerobe for these processes (Stern et al. 2006).
L. salivarius is also able to metabolize bacteriocins, or small peptides with antimicrobial activity (Messaoudi et al. 2013). This property provides L. salivarius with beneficial probiotic properties in humans. Abp118, a bacteriocin of L. salivarius, has been shown to exhibit direct antagonism against human pathogens, such as those that cause foodborne illnesses (Corr et al. 2007). Other bacteriocins produced by this microbe have proven successful in combating the common skin condition, acne (Deidda et al. 2018). Lactic-acid bacterium bacteriocins have increasingly been used as oral and topical antibiotics and disinfectants as well (Messaoudi et al. 2013).
The ecology of specific strains of the genus Lactobacillus have not been studied. Lactobacilli have been found to inhabit the gastrointestinal tract of mammals and thus are part of the gut microbiota. These gut microbiota, when compared to “germ-free” animals, have shown to have substantial influence over the physiology, immunology, and resistance to pathogens of their host (Walter, 2008). They can persist in the stomach, small intestine, or large intestine. The Lactobacilli that inhabit the gut must be well-adapted to their habitats in order to persist and have an impact on their host. L. salivarius has not proven to be able to permanently reside in the gut and thus have lasting effects on the physiology or immunology of its host. Seven-day consumption of the probiotic, L. salivarius, is enough for the bacteria to establish and flourish in the human intestinal tract only transiently (Bonetti et al. 2002).
L. salivarius has proved to be an effective probiotic with at least temporary influence on gut microbiota. The bacteria can reduce host colonization by pathogenic bacteria (Ayala et al. 2017). L. salivarius L28 possesses the ability to fight against several foodborne pathogens, including Escherichia coli O157:H7, Salmonella spp., and Listeria monocytogenes (Ayala et al. 2017). This strain L28 has been isolated from ground beef and its genome was analyzed to pinpoint its specific antagonistic mechanisms or unique genetic markers (Ayala et al. 2017). Tests revealed potential virulence factors and potential genes for tetracycline resistance. In addition, inducing factors for bacteriocin synthesis were found, which explain how L28 can kill or inhibit closely related bacteria (Ayala et al. 2017).
8. Current Research
Today’s research on Lactobacillus salivarius is focused on how this bacterium can serve as an alternative treatment for a variety of human ailments and diseases (Deidda et al. 2018, Peran et al. 2005, Iwamoto et al. 2010). Further studies are also being conducted on the genome sequences of different strains of L. salivarius to determine possible probiotic benefits (Chiu et al. 2017, Corr et al. 2007).
a. Acne treatment
New and promising research has been conducted to demonstrate the health and wellness benefit of L. salivarius in humans. A common discovery in recent research is the capability of secreted bacteriocins from L. salivarius in fighting human diseases and pathogens. Recent studies have discovered the antibacterial and anti-inflammatory properties of the species in combating acne (Deidda et al. 2018). When placed with Propionibacterium acnes, the microbe responsible for skin inflammation due to its secretion of the chemokine Interleukin-8 (IL-8), L. salivarius was able to inhibit IL-8 release through bacteriocin secretion. These novel results are a key step towards the development of new, natural and potentially more effective acne treatments compared to previous topical and oral antibiotics (Deidda et al. 2018).
b. Probiotic use
Current research has also been conducted to test the ability of L. salivarius to act as a fermented dairy product and probiotic. Two sequenced strains of L. salivarius ‒ BCRC 14759 and BCRC 12574 ‒ have shown high levels of exopolysaccharides (EPS) (Chiu et al. 2017). EPS are known to provide several health benefits and are a major component of fermented milk. Both of these sequenced strains also contained genes that increase binding affinity of human bile salts, which may aid in digestion (Chiu et al. 2017). There is no evidence of horizontal gene transfer with other bacteria, furthering its usability (Chiu et al. 2017). Evidence shows L. salivarius is a strong and versatile candidate to be used as a fermented dairy product and probiotic.
c. Fighting against foodborne illness
Previous research has demonstrated the ability of L. salivarius to promote the health of human hosts and fight pathogenic infection with its probiotic properties. L. salivarius has been shown to be effective in reducing the foodborne pathogen Listeria monocytogenes in mice (Corr et al. 2007). L. salivarius secretes the bacteriocin Abp118, which exhibits direct antagonism against the foodborne pathogen. This mechanism could possibly assist in treating foodborne illnesses in humans, gradually replacing the use of antibiotics, which bacteria are becoming increasingly resistant to (Corr et al. 2007).
d. Inflammatory Bowel Disease ulcerative colitis treatment
L. salivarius is also currently used in studies as a potential treatment for the Inflammatory Bowel Disease ulcerative colitis. Colitic rats treated with the probiotic showed recovery of the inflamed tissue of the gut (Peran et al. 2005). Treated rats also showed lower numbers of precursor molecules known to contribute to inflammation, and a rise in beneficial chemicals that are typically depleted due to IBD. The model of the disease studied in rats is similar to that which affects humans; future studies with human subjects and more research on the exact mechanisms of the probiotic on the gut may contribute to the development of alternative treatments for people with IBD (Peran et al. 2005).
e. Halitosis treatment
Studies show L. salivarius can improve the degree of halitosis and clinically associated conditions in those with halitosis (Iwamoto et al. 2010). Subjects with halitosis were given a oral dosage of L. salivarius daily and assessed at 2 and 4 weeks. Oral administration of this probiotic bacteria decreased oral malodor parameters at 2 weeks and scores for an organoleptic test in subjects with physiologic halitosis. Bleeding with probing decreased at 4 weeks for subjects with pathologic halitosis (Iwamoto et al. 2010). The oral bacteria that produce the malodorant tongue biofilms, and are supposedly affected by ingesting L. salivarius, are not fully understood. The specific mechanisms of L. salivarius in this process has yet to be further explored.
 Ayala, D. I., Cook, P. W., Campos, D. L., Brashears, M. M., den Bakker, H., & Nightingale, K. K. (2017). Draft Genome Sequence of Lactobacillus salivarius L28 Isolated from Ground Beef. Genome Announcements, 5(39), e00955–17. http://doi.org/10.1128/genomeA.00955-17
 Bonetti, A., Morelli, L., & Campominosi, E. (2002). Assessment of the persistence in the human intestinal tract of two probiotic lactobacilli lactobacillus salivarius I 1794 and lactobacillus paracasei I 1688. Microbial Ecology in Health and Disease, 14(4), 229-233. doi:10.1080/08910600310002118
 Chapot-Chartier M. & Kulakauskas S. 2014. Cell wall structure and function in lactic acid bacteria. Microbial Cell Factories 13 (Suppl 1):59.
 Chiu, S. H., Chen, C. C., Wang, L. T., & Huang, L. 2017. Whole-genome sequencing of lactobacillus salivarius strains BCRC 14759 and BCRC 12574.Genome Announcements, 5(47):17.
 Claesson, M. J., Li, Y., Leahy, S., Canchaya, C., van Pijkeren, J. P., Cerdeño-Tárraga, A. M., … O’Toole, P. W. (2006). Multireplicon genome architecture of Lactobacillus salivarius. Proceedings of the National Academy of Sciences of the United States of America, 103(17), 6718–6723.
 Corr, S. C., Y. Li, C. U. Riedel, P. W. Otoole, C. Hill, & C. G. M. Gahan. 2007. Bacteriocin Production as a Mechanism for the Antiinfective Activity of Lactobacillus Salivarius UCC118. Proceedings of the National Academy of Sciences 104(18):7617–7621.
 Deidda, F., Amoruso, A., Nicola, S., Graziano, T., Pane, M., & Mogna, L. 2018. New Approach in Acne Therapy: A Specific Bacteriocin Activity and a Targeted Anti IL-8 Property in Just 1 Probiotic Strain, the L. salivarius LS03. Journal of clinical gastroenterology. 1-4.
 European Bioinformatics Institute Protein Information Resource SIB Swiss Institute of Bioinformatics. (n.d.). European Bioinformatics Institute. Retrieved September 19, 2018, from https://www.uniprot.org/taxonomy/1624
 Iwamoto, T., Nao S., Kazunari T., Toru T., and Takao H. 2010. Effects of Probiotic Lactobacillus Salivarius WB21 on Halitosis and Oral Health: an Open-Lab l Pilot Trial. Oral Surgery, Oral Medicine, Oral Pathology, Oral
 Kang, M., Lim, H., Oh, J., Lim, Y., Wuertz-Kozak, K., Harro, J. M., . . . Achermann, Y. (2017). Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus. Pathogens and Disease,75(2). doi:10.3897/bdj.4.e7720.figure2f
 Kuratsu M, Hamano Y, Dairi T. 2010 Analysis of the Lactobacillus metabolic pathway. Appl. Environ. Microbiol.76, 7299–7301.
 Macho Fernandez E, Valenti V, Rockel C, Hermann C, Pot B, Boneca IG, Grangette C. 2011. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut (60):1050-1059. Radiology, and Endodontology 110(2):201–208.
 Messaoudi S, Manai M, Kergourlay G, Prévost H, Connil N, Chobert J-M, Dousset X. Lactobacillus salivarius: bacteriocin and probiotic activity. Food Microbiol. 2013;36(2):296–304.
 Peran, L., Camuesco, D., Comalada, M., Nieto, A., Concha, A., Diaz-Ropero, M. P., … Galvez, J. 2005. Preventative effects of a probiotic, Lactobacillus salivarius ssp. salivarius, in the TNBS model of rat colitis. World Journal of Gastroenterology : WJG11 (33):5185–5192.
 Raftis, EJ, Forde, BM., Claesson MJ., O’Toole PW. (2014) Unusual genome complexity in Lactobaccilus salivarius JCM1046. Neurology and Neuroscience Reports., U.S. National Library of Medicine.
 Seol, Jun-Sang HamHyoun-Wook KimKuk-Hwan, and Aera. (2011). Genome Sequence of Lactobacillus Salivarius NIAS840, Isolated from Chicken Intestine. Journal of Bacteriology, American Society for Microbiology Journals.
 Stern, N. J., Svetoch, E. A., Eruslanov, B. V., Perelygin, V. V., Mitsevich, E. V., Mitsevich, I. P., … Seal, B. S. (2006). Isolation of a Lactobacillus salivarius Strain and Purification of Its Bacteriocin, Which Is Inhibitory to Campylobacter jejuni in the Chicken Gastrointestinal System. Antimicrobial Agents and Chemotherapy, 50(9), 3111–3116.
 Walter, J. (2008). Ecological role of lactobacilli in the gastrointestinal tract: Implications for fundamental and biomedical research.Applied and Environmental Microbiology, 74(16), 4985-4996. doi:10.1128/AEM.00753-08
 Wang R., Jiang L., Zhang M., Zhao L., Hao Y., Guo H., Sang Y., Zhang H. & Ren F. 2017. The Adhesion of Lactobacillus salivarius REN to a Human Intestinal Epithelial Cell Line Requires S-layer Proteins. Sci. Rep 7:44029