Biology:Lactococcus lactis

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Short description: Species of bacterium

Lactococcus lactis
Lactococcus lactis.jpg
Scientific classification edit
Domain: Bacteria
Phylum: Bacillota
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Lactococcus
Species:
L. lactis
Binomial name
Lactococcus lactis
(Lister 1873)
Schleifer et al. 1986
Subspecies

L. l. cremoris
L. l. hordniae
L. l. lactis
L. l. lactis bv. diacetylactis
L. l. tructae

Lactococcus lactis is a gram-positive bacterium used extensively in the production of buttermilk and cheese,[1] but has also become famous as the first genetically modified organism to be used alive for the treatment of human disease.[2] L. lactis cells are cocci that group in pairs and short chains, and, depending on growth conditions, appear ovoid with a typical length of 0.5 - 1.5 µm. L. lactis does not produce spores (nonsporulating) and are not motile (nonmotile). They have a homofermentative metabolism, meaning they produce lactic acid from sugars. They've also been reported to produce exclusive L-(+)-lactic acid.[3] However,[4] reported D-(−)-lactic acid can be produced when cultured at low pH. The capability to produce lactic acid is one of the reasons why L. lactis is one of the most important microorganisms in the dairy industry.[5] Based on its history in food fermentation, L. lactis has generally recognized as safe (GRAS) status,[6][7] with few case reports of it being an opportunistic pathogen.[8][9][10]

Lactococcus lactis is of crucial importance for manufacturing dairy products, such as buttermilk and cheeses. When L. lactis ssp. lactis is added to milk, the bacterium uses enzymes to produce energy molecules (ATP), from lactose. The byproduct of ATP energy production is lactic acid. The lactic acid produced by the bacterium curdles the milk, which then separates to form curds that are used to produce cheese.[11] Other uses that have been reported for this bacterium include the production of pickled vegetables, beer or wine, some breads, and other fermented foodstuffs like soymilk kefir, buttermilk, and others.[12] L. lactis is one of the best characterized low GC Gram positive bacteria with detailed knowledge on genetics, metabolism and biodiversity.[13][14]

L. lactis is mainly isolated from either the dairy environment, or plant material.[15][16][17] Dairy isolates are suggested to have evolved from plant isolates through a process in which genes without benefit in the rich milk were lost or downregulated.[14][18] This process, called genome erosion or reductive evolution, has been described in several other lactic acid bacteria.[19][20] The proposed transition from the plant to the dairy environment was reproduced in the laboratory through experimental evolution of a plant isolate that was cultivated in milk for a prolonged period. Consistent with the results from comparative genomics (see references above), this resulted in L. lactis losing or downregulating genes that are dispensable in milk and the upregulation of peptide transport.[21]

Hundreds of novel small RNAs were identified by Meulen et al. in the genome of L. lactis MG1363. One of them, LLnc147, was shown to be involved in carbon uptake and metabolism.[22]

Cheese production

L. lactis subsp. lactis (formerly Streptococcus lactis)[23] is used in the early stages for the production of many cheeses, including brie, camembert, Cheddar, Colby, Gruyère, Parmesan, and Roquefort.[24] The state Assembly of Wisconsin, also the number one cheese-producing state in the United States, voted in 2010 to name this bacterium as the official state microbe; it would have been the first and only such designation by a state legislature in the nation,[25] however the legislation was not adopted by the Senate.[26] The legislation was introduced in November 2009 as Assembly Bill 556 by Representatives Hebl, Vruwink, Williams, Pasch, Danou, and Fields; it was cosponsored by Senator Taylor.[27] The bill passed the Assembly on May 15, 2010, and was dropped by the Senate on April 28.[27]

The use of L. lactis in dairy factories is not without issues. Bacteriophages specific to L. lactis cause significant economic losses each year by preventing the bacteria from fully metabolizing the milk substrate.[24] Several epidemiologic studies showed the phages mainly responsible for these losses are from the species 936, c2, and P335 (all from the family Siphoviridae).[28]

Therapeutic benefits

The feasibility of using lactic acid bacteria (LAB) as functional protein delivery vectors has been widely investigated.[29] Lactococcus lactis has been demonstrated to be a promising candidate for the delivery of functional proteins because of its noninvasive and nonpathogenic characteristics.[30] Many different expression systems of L. lactis have been developed and used for heterologous protein expression.[31][32][33]

Lactose fermentation In one study that sought to prove that some fermentation produced by L. lactis can hinder motility in pathogenic bacteria, the motilities of Pseudomonas, Vibrio, and Leptospira strains were severely disrupted by lactose utilization on the part of L. lactis.[34] Using flagellar Salmonella as the experimental group, the research team found that a product of lactose fermentation is the cause of motility impairment in Salmonella. It is suggested that the L. lactis supernatant mainly affects Salmonella motility through disruption of flagellar rotation rather than through irreversible damage to morphology and physiology. Lactose fermentation by L. lactis produces acetate that reduces the intracellular pH of Salmonella, which in turn slows the rotation of their flagella.[35][36] These results highlight the potential use of L. lactis for preventing infections by multiple bacterial species.

Secretion of Interleukin-10 Genetically engineered L. lactis can secrete the cytokine interleukin-10 (IL-10) for the treatment of inflammatory bowel diseases (IBD), since IL-10 has a central role in downregulating inflammatory cascades[37] and matrix metalloproteinases.[38] A study by Lothar Steidler and Wolfgang Hans[39] shows that in situ synthesis of IL-10 by genetically engineered L. lactis requires much lower doses than systemic treatments like antibodies to tumor necrosis factor (TNF) or recombinant IL-10.

The authors propose two possible routes by which IL-10 can reach its therapeutic target. Genetically engineered L. lactis may produce murine IL-10 in the lumen, and the protein may diffuse to responsive cells in the epithelium or the lamina propria. Another route involves L. lactis being taken up by M cells because of its bacterial size and shape, and the major part of the effect may be due to recombinant IL-10 production in situ in intestinal lymphoid tissue. Both routes may involve paracellular transport mechanisms that are enhanced in inflammation. After transport, IL-10 may directly downregulate inflammation. In principle, this method may be useful for intestinal delivery of other protein therapeutics that are unstable or difficult to produce in large quantities and an alternative to the systemic treatment of IBD.[citation needed]

Tumor-suppressor through Tumor metastasis-inhibiting peptide KISS1 Another study, led by Zhang B, created a L. lactis strain that maintains a plasmid containing a tumor metastasis-inhibiting peptide known as KISS1.[40] L. lactis NZ9000 was demonstrated to be a cell factory for the secretion of biologically active KiSS1 protein, exerting inhibition effects on human colorectal cancer HT-29 cells.

KiSS1 secreted from recombinant L. lactis strain effectively downregulated the expression of Matrix metalloproteinases (MMP-9), a crucial key in the invasion, metastasis, and regulation of the signaling pathways controlling tumor cell growth, survival, invasion, inflammation, and angiogenesis.[41][42][43] The reason for this is that KiSS1 expressed in L. lactis activates the MAPK pathway via GPR54 signaling, suppressing NFκB binding to the MMP-9 promoter and thus downregulating MMP-9 expression.[44] This, in turn, reduces the survival rate, inhibits metastasis, and induces dormancy of cancer cells.

In addition, it was demonstrated that tumor growth can be inhibited by the LAB strain itself,[45][46] due to the ability of LAB to produce exopolysaccharides.[47][48] This study shows that L. lactis NZ9000 can inhibit HT-29 proliferation and induce cell apoptosis by itself. The success of this strain's construction helped to inhibit migration and expansion of cancer cells, showing that the secretion properties of L. lactis of this particular peptide may serve as a new tool for cancer therapy in the future.[49]

References

  1. ↑ Madigan, Michael T., ed (2005). Brock Biology of Microorganisms (11th ed.). Prentice Hall. ISBN 978-0-13-144329-7. 
  2. ↑ "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease.". Clin Gastroenterol Hepatol 4 (6): 754–759. 2006. doi:10.1016/j.cgh.2006.03.028. PMID 16716759. 
  3. ↑ Roissart, H. and Luquet F.M. Bactéries lactiques: aspects fondamentaux et technologiques. Uriage, Lorica, France, 1994, vol. 1, p. 605. ISBN:2-9507477-0-1
  4. ↑ Åkerberg, C.; Hofvendahl, K.; Zacchi, G.; Hahn-Hägerdal, B. (1998). "Modelling the influence of pH, temperature, glucose and lactic acid concentrations on the kinetics of lactic acid production by Lactococcus lactis ssp. Lactis ATCC 19435 in whole-wheat flour". Applied Microbiology and Biotechnology 49 (6): 682–690. doi:10.1007/s002530051232. 
  5. ↑ Integr8 – Species search results:
  6. ↑ FDA. "History of the GRAS List and SCOGS Reviews". FDA. https://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASSubstancesSCOGSDatabase/ucm084142.htm. 
  7. ↑ "The lactic acid bacteria, the food chain, and their regulation.". Trends in Food Science & Technology 15 (10): 498–505. November 2004. doi:10.1016/j.tifs.2004.03.003. 
  8. ↑ "Lactic acid bacteria and human clinical infection". Journal of Applied Bacteriology 75 (2): 95–107. August 1993. doi:10.1111/j.1365-2672.1993.tb02753.x. PMID 8407678. 
  9. ↑ Facklam RR, Pigott NE, Collins MD. Identification of Lactococcus species from human sources. Proceedings of the XI Lancefield International Symposium on Streptococci and Streptococcal Diseases, Siena, Italy. Stuttgart: Gustav Fischer Verlag; 1990:127
  10. ↑ "Diagnosis of bacterial endocarditis caused by Streptococcus lactis and assisted by immunoblotting of serum antibodies". J. Infect. 21 (3): 317–8. November 1990. doi:10.1016/0163-4453(90)94149-T. PMID 2125626. 
  11. ↑ "Bacteria Genomes - LACTOCOCCUS LACTIS". http://www.ebi.ac.uk/2can/genomes/bacteria/Lactococcus_lactis.html. 
  12. ↑ Shurtleff, William; Aoyagi, Akiko (2004). "History of Fermented Soymilk and Its Products". https://www.soyinfocenter.com/HSS/fermented_soymilk.php. 
  13. ↑ "Comparative and functional genomics of lactococci.". FEMS Microbiology Reviews 29 (3): 411–33. 2005. doi:10.1016/j.femsre.2005.04.004. PMID 15936843. 
  14. ↑ 14.0 14.1 "Natural diversity and adaptive responses of Lactococcus lactis". Current Opinion in Biotechnology 17 (2): 183–90. 2006. doi:10.1016/j.copbio.2006.02.007. PMID 16517150. 
  15. ↑ "Chromosomal diversity in Lactococcus lactis and the origin of dairy starter cultures.". Genome Biology and Evolution 2: 729–44. 2010. doi:10.1093/gbe/evq056. PMID 20847124. 
  16. ↑ "Genes but Not Genomes Reveal Bacterial Domestication of Lactococcus Lactis.". PLOS ONE 5 (12): e15306. 2010. doi:10.1371/journal.pone.0015306. PMID 21179431. Bibcode: 2010PLoSO...515306P. 
  17. ↑ "Diversity analysis of dairy and nondairy Lactococcus lactis isolates, using a novel multilocus sequence analysis scheme and (GTG)5-PCR fingerprinting.". Applied and Environmental Microbiology 73 (22): 7128–37. 2007. doi:10.1128/AEM.01017-07. PMID 17890345. Bibcode: 2007ApEnM..73.7128R. 
  18. ↑ "Genome-scale genotype-phenotype matching of two Lactococcus lactis isolates from plants identifies mechanisms of adaptation to the plant niche.". Applied and Environmental Microbiology 74 (2): 424–36. 2008. doi:10.1128/AEM.01850-07. PMID 18039825. Bibcode: 2008ApEnM..74..424S. 
  19. ↑ "Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus.". Nature Biotechnology 22 (12): 1554–8. 2004. doi:10.1038/nbt1034. PMID 15543133. 
  20. ↑ "The complete genome sequence of Lactobacillus bulgaricus reveals extensive and ongoing reductive evolution.". Proceedings of the National Academy of Sciences of the United States of America 103 (24): 9274–9. 2006. doi:10.1073/pnas.0603024103. PMID 16754859. Bibcode: 2006PNAS..103.9274V. 
  21. ↑ "Microbial domestication signatures of Lactococcus lactis can be reproduced by experimental evolution.". Genome Research 22 (1): 115–24. 2012. doi:10.1101/gr.121285.111. PMID 22080491. 
  22. ↑ Meulen, Sjoerd B. van der; Jong, Anne de; Kok, Jan (2016-03-03). "Transcriptome landscape of Lactococcus lactis reveals many novel RNAs including a small regulatory RNA involved in carbon uptake and metabolism". RNA Biology 13 (3): 353–366. doi:10.1080/15476286.2016.1146855. ISSN 1547-6286. PMID 26950529. 
  23. ↑ "Transfer of Streptococcus lactis and Related Streptococci to the Genus Lactococcus gen. nov." (PDF). Systematic and Applied Microbiology 6 (2): 183–195. 1985. doi:10.1016/S0723-2020(85)80052-7. ISSN 0723-2020. https://dx.doi.org/10.1016/S0723-2020%2885%2980052-7. 
  24. ↑ 24.0 24.1 "Bacteriophage-resistance systems in dairy starter strains: molecular analysis to application". Antonie van Leeuwenhoek 82 (1–4): 303–21. 2002. doi:10.1023/A:1020639717181. PMID 12369198. 
  25. ↑ Davey, Monica (April 15, 2010). "And Now, a State Microbe.". New York Times. https://www.nytimes.com/2010/04/16/us/16microbe.html. 
  26. ↑ "No State Microbe For Wisconsin". National Public Radio. https://www.npr.org/templates/story/story.php?storyId=126370268. 
  27. ↑ 27.0 27.1 "2009 Assembly Bill 556" (in en). http://docs.legis.wisconsin.gov/2009/proposals/ab556. 
  28. ↑ "Milk contamination and resistance to processing conditions determine the fate of Lactococcus lactis bacteriophages in dairies". Appl Environ Microbiol 70 (12): 7365–71. 2004. doi:10.1128/AEM.70.12.7365-7371.2004. PMID 15574937. Bibcode: 2004ApEnM..70.7365M. 
  29. ↑ "Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination". Appl Microbiol Biotechnol 99 (7): 2967–2977. 2015. doi:10.1007/s00253-015-6498-0. PMID 25750046. 
  30. ↑ "Display of the viral epitopes on Lactococcus lactis: a model for food grade vaccine against EV71". Biotechnology Research International 2013 (11): 4032–4036. 2013. doi:10.1155/2013/431315. PMID 1069289. 
  31. ↑ "10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis". Appl Microbiol Biotechnol 68 (6): 705–717. 2005. doi:10.1007/s00253-005-0107-6. PMID 16088349. 
  32. ↑ "Improved stress tolerance of GroESL-overproducing Lactococcus lactis and probiotic Lactobacillus paracasei NFBC 338". Appl Environ Microbiol 70 (10): 5929–5936. 2004. doi:10.1128/AEM.70.10.5929-5936.2004. PMID 15466535. Bibcode: 2004ApEnM..70.5929D. 
  33. ↑ "Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces". J. Biotechnol. 168 (2): 120–129. 2013. doi:10.1016/j.jbiotec.2013.04.019. PMID 23664884. 
  34. ↑ "A lactose fermentation product produced by Lactococcus lactis subsp. lactis, acetate, inhibits the motility of flagellated pathogenic bacteria". Microbiology 161 (4): 701–707. 2015. doi:10.1099/mic.0.000031. PMID 25573770. 
  35. ↑ "Cytoplasmic pH mediates pH taxis and weak-acid repellent taxis of bacteria". J Bacteriol 145 (3): 1209–1221. 1981. doi:10.1128/JB.145.3.1209-1221.1981. PMID 7009572. 
  36. ↑ "Change in intracellular pH of Escherichia coli mediates the chemotactic response to certain attractants and repellents". J Bacteriol 145 (3): 1196–1208. 1981. doi:10.1128/JB.145.3.1196-1208.1981. PMID 7009571. 
  37. ↑ "Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular aspects". Int. Rev. Immunol. 16 (5–6): 501–522. 1998. doi:10.3109/08830189809043006. PMID 9646174. 
  38. ↑ "Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases". Gastroenterology 115 (3): 573–583. 1998. doi:10.1016/S0016-5085(98)70136-2. PMID 9721154. 
  39. ↑ "Treatment of Murine Colitis by Lactococcus lactis Secreting Interleukin-10". Science 289 (5483): 1352–1355. 2000. doi:10.1126/science.289.5483.1352. PMID 10958782. Bibcode: 2000Sci...289.1352S. 
  40. ↑ "Recombinant Lactococcus lactis NZ9000 secretes a bioactive kisspeptin that inhibits proliferation and migration of human colon carcinoma HT-29 cells". Microbial Cell Factories 15 (1): 102. 2016. doi:10.1186/s12934-016-0506-7. PMID 27287327. 
  41. ↑ "New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression". Biochim Biophys Acta 1825 (1): 29–36. 2012. doi:10.1016/j.bbcan.2011.10.001. PMID 22020293. 
  42. ↑ "Matrix metalloproteinases: regulators of the tumor microenvironment". Cell 141 (1): 52–67. 2010. doi:10.1016/j.cell.2010.03.015. PMID 20371345. 
  43. ↑ "Physiology and pathophysiology of matrix metalloproteases". Amino Acids 41 (2): 271–290. 2011. doi:10.1007/s00726-010-0689-x. PMID 20640864. 
  44. ↑ "The KISS1 metastasis suppressor: mechanistic insights and clinical utility". Frontiers in Bioscience 11: 647–659. 2006. doi:10.2741/1824. PMID 16146758. 
  45. ↑ "Lactic acid bacteria and human health". Annals of Medicine 22 (1): 37–41. 1990. doi:10.3109/07853899009147239. PMID 2109988. 
  46. ↑ "The role of lactic acid bacteria in colon cancer prevention: Mechanistic considerations". Lactic Acid Bacteria: Genetics, Metabolism and Applications. 76. 1999. 391–394. doi:10.1007/978-94-017-2027-4_25. ISBN 978-90-481-5312-1. 
  47. ↑ "An overview of the functionality of exopolysaccharides produced by lactic acid bacteria". Int Dairy J 12 (2–3): 163–171. 2002. doi:10.1016/S0958-6946(01)00160-1. 
  48. ↑ "Physiological function of exopolysaccharides produced by Lactococcus lactis". International Journal of Food Microbiology 64 (1–2): 71–80. 2001. doi:10.1016/S0168-1605(00)00437-2. PMID 11252513. 
  49. ↑ "Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer". BMC Cancer 14: 723. 2014. doi:10.1186/1471-2407-14-723. PMID 25260785. 

External links

Wikidata ☰ Q133598 entry



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