Lactococcus lactis is a Gram-positive bacterium used extensively in the production of buttermilk and cheese, but has also become famous as the first genetically modified organism to be used alive for the treatment of human disease. 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 aso been reported to produce exclusive L-(+)-lactic acid. However, 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. Based on its history in food fermentation, L. lactis has generally recognized as safe (GRAS) status  with few case reports of being an opportunistic pathogen.
Schleifer et al. 1986
L. l. cremoris
L. 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 that then separates to form curds, which are used to produce cheese. Other uses that have been reported for this bacterium include the production of pickled vegetables, beer or wine, some breads, and other fermented foodstuffs, such as soymilk kefir, buttermilk, and others. L. lactis is one of the best characterized low GC Gram positive bacteria with detailed knowledge on genetics, metabolism and biodiversity.
L. lactis is mainly isolated from either the dairy environment or plant material. Dairy isolates are suggested to have evolved from plant isolates through a process in which genes without benefit in the rich medium milk were either lost or down-regulated. This process, also called genome erosion or reductive evolution is also described in several other lactic acid bacteria. 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 down-regulating genes which are dispensable in milk and the up-regulation of peptide transport.
L. lactis subsp. lactis (formerly Streptococcus lactis) is used in the early stages for the production of many cheeses, including brie, camembert, Cheddar, Colby, Gruyère, Parmesan, and Roquefort. 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, however the legislation was not picked up by the Senate. 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. The bill passed the Assembly on May 15, 2010, and was dropped by the Senate on April 28.
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. Several epidemiologic studies showed the phages mainly responsible for these losses are from the species 936, c2, and P335 (all from the family Siphoviridae).
In Shuichi Nakamura’s, Yusuke V. Marimoto, and Seishi Kudo’s study, they seek to prove that some fermentation produced by L.lactis can hinder motility in pathogenic bacteria. Using Salmonella Flagellar as the experimental group, Nakamura’s team found that a product of lactose fermentation is the cause of motility impairment in Salmonella. Acetate is produced through lactose fermentation by L.lactis to interrupt the rotation of their flagella.
Another study, lead by Zhang B, created a L.lactis strain that maintains a plasmid containing a tumor metastasis-inhibiting peptide known as KISS1. Here is another study that that shows how L.lactis can be used to combat diseases. 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 illustrates a hopeful future in Cancer therapy.
- Madigan M, Martinko J (editors). (2005). Brock Biology of Microorganisms (11th ed.). Prentice Hall. ISBN 0-13-144329-1.
- Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L (2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clin Gastroenterol Hepatol. 4 (6): 754–759. doi:10.1016/j.cgh.2006.03.028. PMID 16716759.
- 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
- Åkerberg, C.; Hofvendahl, K.; Zacchi, G.; Hahn-Hä;gerdal, 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.
- Integr8 - Species search results:
- FDA. "History of the GRAS List and SCOGS Reviews". FDA. Retrieved 11 May 2012.
- Wessels, S., Axelsson, L., Bech Hansen, E., De Vuyst, L., Laulund, S., Lähteenmäki, L., Lindgren, S.; et al. (November 2004). "The lactic acid bacteria, the food chain, and their regulation". Trends in Food Science & Technology. 15 (10): 498–505. doi:10.1016/j.tifs.2004.03.003.
- Aguirre M, Collins MD (August 1993). "Lactic acid bacteria and human clinical infection". J. Appl. Bacteriol. 75 (2): 95–107. doi:10.1111/j.1365-2672.1993.tb02753.x. PMID 8407678.
- 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
- Mannion PT, Rothburn MM (November 1990). "Diagnosis of bacterial endocarditis caused by Streptococcus lactis and assisted by immunoblotting of serum antibodies". J. Infect. 21 (3): 317–8. doi:10.1016/0163-4453(90)94149-T. PMID 2125626.
- Lactococcus lactis uses
- Kok, J., Buist, G., Zomer, A. L., van Hijum, S. a F. T., & Kuipers, O. P. (2005). "Comparative and functional genomics of lactococci". FEMS Microbiology Reviews. 29 (3): 411–33. doi:10.1016/j.femsre.2005.04.004.
- van Hylckama Vlieg, Johan E T, Rademaker, J. L. W., Bachmann, H., Molenaar, D., Kelly, W. J., & Siezen, R. J. (2006). "Natural diversity and adaptive responses of Lactococcus lactis". Current Opinion in Biotechnology. 17 (2): 183–90. doi:10.1016/j.copbio.2006.02.007.
- Kelly, W. J., Ward, L. J. H., & Leahy, S. C. (2010). "Chromosomal diversity in Lactococcus lactis and the origin of dairy starter cultures". Genome biology and evolution. 2: 729–44. doi:10.1093/gbe/evq056.
- Passerini, D., Beltramo, C., Coddeville, M., Quentin, Y., Ritzenthaler, P., Daveran-Mingot, M.-L., & Le Bourgeois, P. (2010). "Genes but Not Genomes Reveal Bacterial Domestication of Lactococcus Lactis". PLoS ONE. 5 (12): e15306. doi:10.1371/journal.pone.0015306.
- Rademaker, J. L. W., Herbet, H., Starrenburg, M. J. C., Naser, S. M., Gevers, D., Kelly, W. J., Hugenholtz, J.; et al. (2007). "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. doi:10.1128/AEM.01017-07. PMC . PMID 17890345.
- Siezen, R. J., Starrenburg, M. J. C., Boekhorst, J., Renckens, B., Molenaar, D., & van Hylckama Vlieg, J. E. T. (2008). "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. doi:10.1128/AEM.01850-07. PMC . PMID 18039825.
- Bolotin, A., Quinquis, B., Renault, P., Sorokin, A., Ehrlich, S. D., Kulakauskas, S., Lapidus, A.; et al. (2004). "Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus". Nature Biotechnology. 22 (12): 1554–8. doi:10.1038/nbt1034. PMID 15543133.
- van de Guchte, M., Penaud, S., Grimaldi, C., Barbe, V., Bryson, K., Nicolas, P., Robert, C.; et al. (2006). "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. doi:10.1073/pnas.0603024103. PMC . PMID 16754859.
- Bachmann, H., Starrenburg, M. J. C., Molenaar, D., Kleerebezem, M., & van Hylckama Vlieg, J. E. T. (2012). "Microbial domestication signatures of Lactococcus lactis can be reproduced by experimental evolution". Genome Research. 22 (1): 115–24. doi:10.1101/gr.121285.111. PMC . PMID 22080491.
- 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. PMC . PMID 26950529.
- Chopin MC, Chopin A, Rouault A, Galleron N (1 July 1989). "Insertion and amplification of foreign genes in the Lactococcus lactis subsp. lactis chromosome" (PDF). Appl. Environ. Microbiol. 55 (7): 1769–74. PMC . PMID 2504115.
- Coffey A, Ross RP (2002). "Bacteriophage-resistance systems in dairy starter strains: molecular analysis to application". Antonie Van Leeuwenhoek. 82 (1–4): 303–21. doi:10.1023/A:1020639717181. PMID 12369198.
- Davey, Monica (April 15, 2010). "And Now, a State Microbe". New York Times. Retrieved April 19, 2010.
- "No State Microbe For Wisconsin". National Public Radio. Retrieved 28 October 2011.
- "2009 Assembly Bill 556". docs.legis.wisconsin.gov. Retrieved 2017-11-29.
- Madera C, Monjardin C, Suarez JE (2004). "Milk contamination and resistance to processing conditions determine the fate of Lactococcus lactis bacteriophages in dairies". Appl Environ Microbiol. 70 (12): 7365–71. doi:10.1128/AEM.70.12.7365-7371.2004. PMC . PMID 15574937.
- Nakamura, Shuichi; Morimoto, Yusuke V.; Kudo, Seishi (2015). "A lactose fermentation product produced by Lactococcus lactis subsp. lactis, acetate, inhibits the motility of flagellated pathogenic bacteria". Microbiology. 161 (4): 701–707. doi:10.1099/mic.0.000031.
- Zhang, Bo; Li, Angdi; Zuo, Fanglei; Yu, Rui; Zeng, Zhu; Ma, Huiqin; Chen, Shangwu (2016-06-10). "Recombinant Lactococcus lactis NZ9000 secretes a bioactive kisspeptin that inhibits proliferation and migration of human colon carcinoma HT-29 cells". Microbial Cell Factories. 15. doi:10.1186/s12934-016-0506-7. ISSN 1475-2859. PMC . PMID 27287327.