Higher order taxa
Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae; Lactobacillus
Description and significance
From the genus Lactobacillus, L. jensenii is a "facultatively anaerobic, catalase-negative, none-spore-forming, Gram Positive, rod-shaped" bacteria. This particular strain is one of the predominant species (along with Lactobacillus crispatus) found in the female lower genital tract. Its ability to colonize as a natural vaginal microflora is recently become a high topic of interests to researchers studying prevention of STDs and vaginal bacterias.
HIV/AIDS researchers who are looking for a genetically modifiable container that would express HIV inhibitors (CV-N) find L.jensenii to be of special interest. So, to ensure there would be sufficient expression of CV-N by this bacterium, L. jensenii 1153 genome has been partially sequenced. (See Current Research for more details).
Also, studies that include L.jensenii anaerobic mechanisms of producing H2O2 are hot topics for modern researchers who correlate the high colonization of L.jensenii to low colonizations of vaginal bacterias. (See Ecology for more details)
As of May 2007, L. jensenii 1153 genome has been fully sequenced using shotgun sequencing by the collaboration of Lawrence Berkeley National Lab and Osel: The Bacterio-Therapeutics Company, but the data is yet released to public. For this reason, information on native plasmids nor on its genome is not accesible. Most of the sequencing methods include bacterial colony-based strain typing using PCR-fingerprinting and phylogenetic analysis of the partial 16S rRNA gene. Analysis shows that its genome contains over 1600 ORFs which include "novel cell wall anchor domains, unique signal sequences, powerful promoter elements, and possible sites for chromosomal integration of heterologous genes." Its DNA has low G+C content and produces D-lactic acid as its major product.
Cell structure and metabolism
L. jensenii, like other members of the Lactobacillus, are rod-shaped, anaerobic gram positive microorganisms. It can be differentiated from other species because of the following characteristics: hydrolysis of arginine, production of D-lactate (only), and fermentation of galatose, ribose, and cellobiose, but not of lactose.
As an anaerobe and the member of Lactobacillus - bacteria known for acids production, L. jensenii is responsible for producing acid in the vagina by anaerobic metabolism of glycogen. The glycogen are deposited in the vaginal epithelium cells when there is a high level of estrogen, specifically during menstruation period. The vaginal flora and the surrounding epithelial cells metabolize the glycogen into acetic and lactic acid so that the vaginal pH becomes about 4. The strong concentration of the acidic environment help protect the vagina from harmful pathogens in the environment.
L.jensenii has difficulty when replicating outside the body. As a matter of fact, Lactobacillus jensenii (along with Lactobacillus crispatus and Lactobacillus gasseri) is a natural vaginal strain of bacteria colonized in the biofilms of the vaginal mucosa of healthy females. This particular vaginal lactobacilli contributes to 23% of its colony population (following Lactobacillus crispatus-32%), making it the second most prevalent vaginal lactobilli in the lower female genital tract. This H2O2 producing bacteria contributes to inhibiting anaerobic growth. Combined with acidic environment of pH less than 4.5, Bacterial Vaginosis (BV)'s growth as well as transmission and infections of genital related diseases (gonorrhea, urinary tract infection, and chlamydia) or STDs (HIV) are effectively inhibited. Since semen does decrease the acidic environment of the vagina, studies show that repeated and unprotected intercourse increase risk of BV colonization.
How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
So far, its pathogenicity for men is unknown. As for women, it does not cause disease, but protects host from acquisition of diseases. (See Ecology for more details)
Application to Biotechnology
Research by Beckman and Ames 1998 demonstrate that free radicals and reactive oxygen species (ROS) helps prevent atherosclerosis, diabetes, and cancer. These radicals that form from aerobic respiration while food digestion can damage cells. Food containing antioxidants are able to help quicken the restoration of damaged tissues/cells, therefore, increasing the defense mechanism of the body. Because anaerobic bacteria such as L. jengenii possess anti-oxidant activity, their ability to break down superoxide anion and H2O2 with milk proteins is the highlight of current studies. Researches are concluding "Lactobacillus jensenii strain showed high antioxidant potential...and it had also high content of hydrophobic amino acids, valine, leucine, phenylalanine and tryptophan." The strain's specific amino acid content matters because its hydrophobic properties of its composition are related to the inhibition of peroxidation activities. Because of this property, we may be able to create fermentated milk that can now possess higher antioxidant activity.
Some of the recent researches on Lactobacillus jensenii:
"Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4"
Knowing that HIV enters through cervico-vaginal mucosa, Lactobacillus jensenii, which is known to naturally colonize in the vaginal area, is genetically engineered to secrete two-domain CD4 (2D CD4) proteins. The secreted 2D CD4 binds to anti-CD4 receptor and bound HIV-1 gp120, which shows that the engineering did not affect the L. jensenii proteins structure. Moreover, with the usage of luciferase reproter gene, single-cycle infection assays confirmed that the modified L. jensenii is able to inhibit HIV-1 from infecting target cells. Furthermore, when the bacteria was incubated with recombinant HIV-1HxB2 reporter virus, the infectivity of HeLa cells expressing CD4–CXCR4–CCR5 decreased considerably. The decrease in infectivity of HIV-1 with dosage controlled engineered L. jensenii may be a convenient contraception by using natural occuring colonies of bacteria inside the body to block the transmission of HIV.
Engineered Vaginal Lactobacillus Strain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N
Lactobacillus jensenii has been genetically engineered to produce and secrete peptide that prevents fusion with HIV using S-protein layer secretion pathway. The modification did not affect the phenotype of the bacteria, but rather was integrated stably into the chromosome. This new Lactobacillus CV-N hybrid was capable of inhibiting "CCR5-tropic HIVBaL infectivity in vitro with a 50% inhibitory concentration of 0.3 nM". Genetically engineered L. jensenii was able to proliferate in the vaginas of estrus phase mice as well as secrete this anti-HIV peptide. This may be an inexpensive and convenient way to block HIV infection and/or replication in women.
Inhibition of Neisseria gonorrhoeae by Lactobacillus Species That Are Commonly Isolated from the Female Genital Tract
Four strains (Lactobacillus jensenii, Lactobacillus crispatus, Lactobacillus acidophilus, and Lactobacillus gasseri) of Lactobacillus were studied because of past reports of the possible link between high colonization of Lactobacillus and low risk of gonorrhea. In this experiment, Neisseria species or Escherichia coli strains serving as target organisms and four clinical isolates of N. gonorrhoeae were added at different pH on plates containing heart infusion agar and saline solutions of respective Lactobacillus strains. All four strains were able to inhibit the gonococcal strains at low pH while L. jensenii and L. crispatus was also able to inhibit N. gonnorrhoeae at neutral pH. None of them were able to inhibit E. coli strains, though L. jensenni was able to inhibit Neisseria cinerea. On the quantitative scale of the assay, L. jensenii were particularly most resistant to N. gonorrhoeae in the four strains. The strains were able to use H2O2 as mediator to resist the infection. The paper was able to conclude that the presence of L. jensenii and L. crispatus helps reduce risk of gonorrhoeae.
Enevold Falsen, Christina Pascual, Berit Sjoden, Maria Ohlen and Matthew D. Collins. 1999. Phenotypic and phylogenetic characterization of a novel Lactobacillus species from human sources: description of Lactobacillus iners sp.nov." 'International Journal of Systematic Bacteriology', vol 49, (217–221)
Dean Hamer, Louise McHugh, Margaret McKinney, Chris Richards,Kevin Schully, Laurel Lagenaur and Srinivas Rao. 2006. "Live microbial microbicides for HIV 2006". International Meeting of The Institute of Human Virology Baltimore, USA. 17–21 November, 2006
Diane C. St. Amant,Iris E. Valentin-Bon, and Ann E. Jerse. "Inhibition of Neisseria gonorrhoeae by Lactobacillus Species That Are Commonly Isolated from the Female Genital Tract". Infection and Immunity, December 2002, p. 7169-7171, Vol. 70, No. 12
Xiaowen Liu, Laurel A. Lagenaur, David A. Simpson, Kirsten P. Essenmacher, Courtney L. Frazier-Parker, Yang Liu, Daniel Tsai, Srinivas S. Rao, Dean H. Hamer, Thomas P. Parks, Peter P. Lee, and Qiang Xu. "Engineered Vaginal Lactobacillus Strain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N". Antimicrob Agents Chemother. 2006 October; 50(10): 3250–3259
Theresa L.-Y. Chang, Chia-Hwa Chang, David A. Simpson, Qiang Xu, Patrick K. Martin, Laurel A. Lagenaur, Gary K. Schoolnik, David D. Ho,§ Sharon L. Hillier, Mark Holodniy, John A. Lewicki, and Peter P. Lee. 2003. "Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4". Proc Natl Acad Sci U S A. 2003 September 30; 100(20): 11672–11677
Chang, Chia-Hwa Cheng, J., Frankel, K., Essenmacher, K., Simpson, D., Lagenaur L., Parks, T., Martin, P., Liu, X., Xu, Q., and Lewicki, J., Osel, Inc. "Optimizing Expression of Protein Microbicides in Lactobacilli: Benefits of Genomic Sequencing". Microbicides 2004
E. R. Boskey, K. M. Telsch, K. J. Whaley, T. R. Moench, and R. A. Cone. "Acid Production by Vaginal Flora In Vitro Is Consistent with the Rate and Extent of Vaginal Acidification" Infect Immun. 1999 October; 67(10): 5170–5175.
Edited by Frances Cho, student of Rachel Larsen at UCSD.