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Journal of Biotechnology & Bioresearch

Lactobacillus Rhamnosus, as a Potential Candidate against Candidiasis

Pakdaman BS*

Department of Plant Protection, Faculty of Agriculture, Agricultural Sciences and Natural Resources University of Khuzestan, Iran

*Corresponding author: Pakdaman BS, Department of Plant Protection, Faculty of Agriculture, Agricultural Sciences and Natural Resources University of Khuzestan, Iran

Submission: August 22, 2022;Published: September 01, 2022

Volume4 Issue2
September, 2022


Candidiasis is one of the prevalent reproductive diseases in reproductive-aged women that can be fatal. The disease is caused by Candida spp. Lactobacillus spp. are gram-positive, facultative, non-sporulating and rod-shaped bacteria Generally Recognized as Safe (GRAS) and applied as probiotics. The antifungal activity of Lactobacilli is a controversial subject not well understood. Therefore, it would be interesting to study the antifungal activity of vaginal and uterine strains of Lactobacilli, and to screen for the superior Lactobacillus strains with higher lactic acid production, higher antibacterial as well as antifungal potential, and to improve them via the generation of the transformants that express and secrete the antifungal as well as antibacterial peptides such as metchnikowin.

Keywords:Bio-control; Candida; Metchnikowin; Probacteria; Peptide


Candida species are a major cause of morbidity and mortality worldwide and represent a serious threat to public health [1-3]. These opportunistic pathogens can cause vaginitis, oral candidiasis, cutaneous candidiasis, candidemia, and systemic infections [4]. Candidemia is the most frequent hospital infection accounting for up to 15% of bloodstream infections and Candida spp. are the main causal agents in 50-70% of systemic fungal infections [5-7]. Despite the danger of the disease, the available drugs have not been enough efficient. For example, 90- day survival following the diagnosis of candidemia varies between 55% and 70%, depending on the underlying condition of the patient and the specific species causing infection [8]. The occurrence of human immunodeficiency disease, the use of immunosuppressive medicaments applied in neoplastic surgeries, diabetics, dialysis, severe burns, abdominal surgery, and the use of corticosteroids, cancer chemotherapeutics, and antibacterial antibiotics [9]. Most recently the bacterial flora of uterus in healthy females and ill females has been reviewed [10], where significant differences in the diversity of the bacteria have been noticed [10].

Based on this valuable review, Bacillus, Blautia, Desulfosporosinus, and Parabacterioides are only found in healthy uterus. Burkholderia, Chitinopagaceous bacteria, Pelomonas and Rhodanobacter are associated with female infertility. Moraxellaceous bacteria, Streptococcaceous bacteria, Sphingobium and Vagococcus are especially found in the uterus of the females suffering from endometriosis. Anaerococcus and Parvimonas are only found in the uteri with chronic endometriosis, while Euryarchaeota only in the uteri with polyps. The bacteria from the genera Anarostipes, Anaerotruncus, Arthrospira, Cloacibacterium, Peptoiphilus, Porphyromonas, Ruminococcus and Treponema are only isolated from uteri with cancer [10].

Although bacteria only found in healthy uteri seem to be the most proper choices for the biological control of uterus candidiasis, however, only bacteria from the genus Lactobacillus are found in all uteri but those with cancer. It seems that these bacteria can survive under various physiological conditions inside uteri, and therefore, these bacteria can be selected for engineering the bacterial flora of uterus. Recently a strain of Lactobacillus rhamnosus PBL005 has been known to be of probiotic potentials in gynecological health. The bacterium reduces the level of pathogenic bacteria such as Propionibacterium acnes and Streptococcus agalactiae [11]. Additionally, women vaginally colonized with Lactobacillusdominated microflora are less likely to acquire HIV from their male partners [12] and indicate reduced viral shedding into the lower FRT [13] that could protect against the sexual transmission of HIV to their male partners and to vaginally delivered neonates [14]. The lactic acid produced at physiological concentrations exhibits a broad-spectrum HIV viricidal activity [15]. Although both enantiomers of the acid exhibit similar viricidal activity against HIV-1 at 1% (w/w), however, L-lactic acid is 17-fold more potent than the D-isomer at the threshold concentration of 0.3% [15]. Similarly, women with dominant vaginal Lactobaclli are less likely to be infected with herpes simplex virus-2, HSV-2 [13].

While most of these gram-positive bacteria of the genus are generally recognized as safe (GRAS) [16], they have been reported as effective antagonists of pathogenic fungi [17]. The role of lactobacillus species as a barrier to prevent vulvovaginal candidiasis diseases caused by Candida species is controversial [18]. Based on in vitro studies, Lactobacilli are believed to play this preventive role either by the production of antimicrobial factors or via the competition with Candida species for adhesion sites on the mucosa [19]. Regarding the mechanism of the antagonism, there is evidence that the growth of Candida albicans is inhibited by lactic acid produced by lactobacilli at low pH [20] or is not inhibited [21]. Vaginal Candida species demonstrate different levels of acid tolerance and adapt to low acidity through several mechanisms, including high plasma membrane proton pump activity [22]. Thus, the ability of lactic acid to inhibit Candida growth may depend on the level of acid tolerance of an individual species.

Despite these in vitro data, epidemiological studies do not support a protective role for vaginal Lactobacillus species against vulvovaginal candidiasis. Colonization of the vagina with Candida species is more common in the women with BV [23]. Furthermore, a prospective study has indicated that vaginal Lactobacilli do not protect against vulvovaginal candidiasis while BV affords protection [24]. Natural antimicrobial peptides are considered as inspiration for design of a new generation antifungal compounds [25], a goal that necessitates the innovation of new methodologies for the practically effective application of antifungal peptides. It is possible to increase the antagonistic potential of L. rhamnosus PBL005 via generation of the transformants that express antifungal peptide transgenes and secret the antifungal peptides against Candida spp. Such an activity could be an important step toward the application of the bacterial strain in the practical restructuring the microbial flora of the vagina and uterus. Therefore, it would be interesting to isolate Lactobacillus rhamnosus strains, screen them for their antibacterial activity against pathogenic endometrial bacteria and to test their antifungal activity against pathogenic Candida spp. The antimicrobial peptides can be applied in the enhancement of their biological control potential against microbial pathogens. One of these peptides is metchnikowin, a 26 amino acid proline-rich peptide produced by Drosophila that exhibits antimicrobial activity against fungi as well as gram negative bacteria [26].


  1. Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, et al. (2014) Epidemiology and outcomes of invasive candidiasis due to non-albicans species of candida in 2,496 patients: Data from the Prospective Antifungal Therapy (PATH) registry 2004-2008. PLoS ONE 9(7): e101510.
  2. Matthaiou DK, Christodoulopoulou T, Dimopoulos G (2015) How to treat fungal infections in ICU patients. BMC Infect Dis15: 205.
  3. Pappas PG, Kaufman CA, Andes DR, Clancy CJ, Marr KA, et al. (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the infectious disease’s society of America. Clinical Infectious Diseases 62(4): e1-e50.
  4. Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, et al. (2012) Candida albicans-epithelil interactions: Dissecting the role of active penetration, induced endocytosis and host factors on the infection process. PLoS One 7(5): e36952.
  5. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, et al. (2012) ESCMID guideline for the diagnosis and management of Candida disease 2012: Non-neutropenic adult patients. Clinical Microbiology and Infection 8: 19-37.
  6. Lionakis MS, Netea MG (2013) Candida and host determinants of susceptibility to invasive candidiasis. PloS Pathogens 9: e1003079.
  7. Barchiesi F, Orsetti E, Osimani P, Catassi C, Santelli F, et al. (2016) Factors related to outcome of bloodstream infections due to Candida parapsilosis complex. BMC Infectious Diseases 16: 387.
  8. Pfaller M, Neofytos D, Diekema D, Azie N, Krisesche HU, et al. (2012) Epidemiology and outcomes of candidemia in 3648 patients: Data for the Prospective Antifungal Therapy (PATH Alliance®) register, 2004-2008. Diagn Microbiol Infect Dis 74(4): 323-331.
  9. Kotthoff-Burrel E (2019) Candidemia (blood infection) and other Candida infections. Am J Respir Crit Care Med 200: 9-10.
  10. Molina NM, Sola-Leyva A, Saez-Lara MJ, Plaza-Diaz J, Tubić-Pavlović A, et al. (2020) New opportunities for endometrial health by modifying uterine microbial composition: Present or future? Biomolecules 10(4): 593.
  11. Chenoll E, Moreno I, Sánchez M, Garcia-Grau I, Silva Á, et al. (2019) Selection of new probiotics for endometrial health. Front Cell Infect Microbiol 9: 114.
  12. Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, et al. (1998) Bacterial vaginosis and disturbances of vaginal flora: Association with increased acquisition of HIV. AIDS 12(13): 1699-1706.
  13. Borgodorff H, Tsivtsivadze R, Verhelst R, Marzorati M, Jurriaans S, et al. (2014) Lactobacillus-dominated cervicovaginal microbiota associated with reduced HHIV/STI prevalence and genital HIV viral load in African women. ISME J 8(9): 1781-1793.
  14. Tachedjian G, Aldunate M, Bradshaw CS, Cone RA (2017) The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 168(9-10): 782-792.
  15. Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza T, et al. (2013) Vaginal concentrations of lactic acid potently inactivate HIV. J Antimicrob Chemother 68(9): 2015-2025.
  16. Böhmer N (2013) Food-grade Lactobacilli expression systems for recombinant enzymes, Institute for Food Science and Biotechnology, University of Hohenheim, Germany.
  17. Kerr JR (1999) Bacterial inhibition of fungal growth and pathogenicity. Microbial Ecology in Health and Disease 11: 129-142.
  18. Tachedjian G, Aldunate M, Bradshaw CS, Cone RA (2017) The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 168: 782-792.
  19. Morales DK, Hogan DA (2010) Candida albicans interactions with bacteria in the context of human health and disease. PLoS Pathog 6(4): e1000886.
  20. Krasner RI, Young G, Yudkofsky PL (1956) Interactions of oral strains of Candida albicans and Lactobacilli. Journal of Bacteriology 72: 525-529.
  21. Juarez Tomas MS, Saralegui Duhart CI, De Gregorio PR, Pingitore EV, Macias ME (2011) Urogenital pathogen inhibition and compatibility between vaginal Lactobacillus strains to be considered as probiotic candidates. Eur J Obstet Gynecol Reprod Biol 159(2): 399-406.
  22. Cunha DV, Salazar SB, Lopes MM, Mira NP (2017) Mechanistic insights underlying tolerance to acetic acid in vaginal Candida glabrata clinical isolates. Front Microbiol 8: 259.
  23. Van de Wijgert JH, Borgodorff H, Verhelst R, Crucitti T, Francis S, et al. (2014) The vaginal microbiota: What have we learned after a decade of molecular characterization? PLoS ONE 9(8): e105998.
  24. McClelland RS, Richardson BA, Hassan WM, Graham SM, Kiarie J, et al. (2009) Prospective study of vaginal bacterial flora and other risk factors for vulvovaginal candidiasis. J Infect Dis 199(12): 1883-1890.
  25. Bondaryk M, Staniszewska M, Zieliska P, Urbaczyk-Lipkowska (2017) Natural antimicrobial peptides as inspiration for design of a new generation antifungal compounds. J Fungi (Basel) 3(3): 46.
  26. Levashina EA, Ohresser S, Bulet P, Reichhart JM, Hetru C, et al. (1995) Metchnikowin, a novel immune-inducible proline-rich peptide from drosophila with antibacterial and antifungal properties. Eur Biochem 233(2): 694-700.

© 2022 Pakdaman BS. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.