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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Vulvovaginal Candidiasis | Research article

Inhibitory effects of Lactobacillus casei Shirota against both Candida auris and Candida spp. isolates that cause vulvovaginal candidiasis and are resistant to antifungals

Authors: Aline Lorenzoni Paniágua, Amabel Fernandes Correia, Lívia Custódio Pereira, Bruna Maciel de Alencar, Fabiana Brandão Alves Silva, Rosane Mansan Almeida, Yanna Karla de Medeiros Nóbrega

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Vulvovaginal candidiasis (VVC), the second leading cause of genital infection in women of reproductive age, is caused by yeasts of the genus Candida. Treatment is usually empirical and performed with azoles, which have shown increasing ineffectiveness due to resistance from these species. This therapeutic challenge has led to the search for new treatment strategies. Lactobacillus spp. produce several components with microbicidal effects, such as lactic acid. These species are the main components of a healthy vaginal microbiota and have been used as probiotics. The aim of this work was to investigate the in vitro inhibitory effects of Lactobacillus casei Shirota on both the Candida spp. that cause VVC and on C. auris.

Methods

The microbicidal effects of L. casei Shirota on the main VVC-causing species, C. albicans, C. tropicalis, C. norvegensis and C. parapsilosis, in addition to C. auris were investigated by counting the Colony-forming Units (CFUs) after cocultivation. The antifungal activity of lactic acid against these Candida strains was assessed using the microtiter broth dilution method to determine the minimum inhibitory concentrations (MICs). The effects of L. casei Shirota on hyphal and early biofilm formation was measured by optical microscopy.

Results

L. casei Shirota showed inhibitory action against all tested Candida spp., ranging from 66.9 to 95.6% inhibition depending on the species. This inhibition is possibly related to the production of lactic acid, since lactic acid has shown microbicidal action against these same Candida spp. at a concentration of 5 mg/mL, which corresponds to half of the normal physiological concentration. In addition, L. casei Shirota was able to reduce the formation of C. albicans hyphae and early biofilms, showing strong anti-Candida effects.

Conclusions

These results suggest that L. casei Shirota has antifungal activity against the Candida species that cause VVC. L. casei also has microbicidal action against C. auris.

Rodríguez-Cerdeira C, Gregorio MC, Molares-Vila A, López-Barcenas A, Fabbrocini G, Bardhi B, et al. Biofilms and vulvovaginal candidiasis. Colloids Surf B Biointerfaces. 2019;174:110–25. https://doi.org/10.1016/j.colsurfb.2018.11.011.CrossRefPubMed

Yano J, Sobel JD, Nyirjesy P, Sobel R, Williams VL, Yu Q, et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC Womens Health. 2019;19:48. https://doi.org/10.1186/s12905-019-0748-8.CrossRefPubMedPubMedCentral

Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016;42(6):905–27. https://doi.org/10.3109/1040841X.2015.1091805.CrossRefPubMed

Deorukhkar SC, Saini S, Mathew S. Non-C. albicans Candida infection: an emerging threat; 2014. https://doi.org/10.1155/2014/615958.CrossRef

Makanjuola O, Bongomin F, Fayemiwo SA. An update on the roles of Non-C. albicans Candida species in vulvovaginitis. J Fungi (Basel). 2018;4(4):121. https://doi.org/10.3390/jof4040121.CrossRef

Behtash A, Nafisi S, Maibach H. New generation of fluconazole: a review on existing researches and technologies. Curr Drug Deliv. 2017;14(1):2–15. https://doi.org/10.2174/1567201813666160502125620.CrossRefPubMed

Sobel JD, Sobel R. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species. Expert Opin Pharmacother. 2018;19(9):971–7. https://doi.org/10.1080/14656566.2018.1476490.CrossRefPubMed

Haegler P, Joerin L, Krähenbühl S, Bouitbir J. Hepatocellular Toxicity of Imidazole and Triazole Antimycotic Agents. Toxicological Sciences. 2017;157(1):183–95. https://doi.org/10.1093/toxsci/kfx029.

Marx-Stoelting P, Constanze K, Braeuning A. The Connection of Azole Fungicides with Xeno-Sensing Nuclear Receptors Drug Metabolism and Hepatotoxicity. Cells. 2020;9(5):1192. https://doi.org/10.3390/cells9051192.

10.

Wagner D, Johnson SJ. Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans. J Biomed Sci. 2012;19(1):58. https://doi.org/10.1186/1423-0127-19-58.CrossRefPubMedPubMedCentral

11.

Leão MVP, Tavares TAA, Gonçalves e Silva CR, dos Santos SSF, Junqueira JC, de Oliveira LD, et al. Lactobacillus rhamnosus intake can prevent the development of Candidiasis. Clin Oral Investig. 2018;22(7):2511–8. https://doi.org/10.1007/s00784-018-2347-8.CrossRefPubMed

12.

Matsubara VH, Bandara HMHN, Mayer MPA, Samaranayake LP. Probiotics as antifungals in mucosal candidiasis. Clin Infect Dis. 2016;62(9):1143–53. https://doi.org/10.1093/cid/ciw038.CrossRefPubMed

13.

Kovachev S. Defence factors of vaginal lactobacilli. Crit Rev Microbiol. 2018;44(1):31–9. https://doi.org/10.1080/1040841X.2017.1306688.

14.

Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol. 2017;168(9-10):782–92. https://doi.org/10.1016/j.resmic.2017.04.001.CrossRefPubMed

15.

Petrova MI, Lievens E, Shweta M, Imholz N, Lebeer S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol. 2015;6. https://doi.org/10.3389/fphys.2015.00081.

16.

Petrova MI, Gregor R, Vaneechoutte M, Lebeer S. Lactobacillus iners : Friend or Foe?. Trends Microbiol. 2017;25(3):182–91. https://doi.org/10.1016/j.tim.2016.11.007.

17.

Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016;214(1):15–21. https://doi.org/10.1016/j.ajog.2015.06.067.CrossRefPubMed

18.

Spivak ES, Hanson KE, Kraft CZ. Candida auris: an Emerging Fungal Pathogen. J Clin MicrobiolC. 2018;56(2). https://doi.org/10.1128/JCM.01588-17.

19.

Rossoni RD, de Barros PP, Mendonça IDC, Medina RP, Silva DHS, Fuchs BB, Junqueira JC, Mylonakis E. The Postbiotic Activity of Lactobacillus paracasei 28.4 Against Candida auris. Front Cell Infect Microbiol. 2020;10. https://doi.org/10.3389/fcimb.2020.00397.

20.

Pfaller MA, Haturvedi V, Espinel-Ingroff A, Ghannoum MA, Gosey LL, Odds FC, et al. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard — second edition serving the world ’ s medical science community through voluntary consensus. 2002.

21.

Kang MS, Lim HS, Oh JS, Lim YJ, Wuertz-Kozak K, Harro JM, et al. Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus. Pathog Dis. 2017;75(2). https://doi.org/10.1093/femspd/ftx009.

22.

Hong SK, Chang BK, Song SH, Kim EC. Use of MALDI-TOF MS technique for rapid identification of bacteria from positive blood cultures. Indian J Med Microbiol. 2014;32(4):419–22. https://doi.org/10.4103/0255-0857.142261.CrossRefPubMed

23.

O’hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013;8(11):e80074. https://doi.org/10.1371/journal.pone.0080074.CrossRefPubMedPubMedCentral

24.

Kornitzer D. Regulation of Candida albicans hyphal morphogenesis by endogenous signals. J Fungi (Basel). 2019;5(1):21. https://doi.org/10.3390/jof5010021.CrossRef

25.

Lagree K, Mon HH, Mitchell AP, Ducker WA. Impact of surface topography on biofilm formation by Candida albicans. PLoS One. 2018;13(6):e0197925. https://doi.org/10.1371/journal.pone.0197925.CrossRefPubMedPubMedCentral

26.

Kim J-M, Park YJ. Probiotics in the prevention and treatment of postmenopausal vaginal infections: review article. J Menopausal Med. 2017;23(3):139–45. https://doi.org/10.6118/jmm.2017.23.3.139.CrossRefPubMedPubMedCentral

27.

Mirmonsef P, Spear GT. The barrier to HIV transmission provided by genital tract Lactobacillus colonization. Am J Reprod Immunol. 2014;71(6):531–6. https://doi.org/10.1111/aji.12232.CrossRefPubMed

28.

Lo HJ, Köhler JR, Didomenico B, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997;90(5):939–49. https://doi.org/10.1016/S0092-8674(00)80358-X.CrossRefPubMed

29.

Witchley JN, Penumetcha P, Abon NV, Woolford CA, Mitchell AP, Noble SM. Candida albicans morphogenesis programs control the balance between gut commensalism and invasive infection. Cell Host Microbe. 2019;25:432–443.e6. https://doi.org/10.1016/j.chom.2019.02.008.CrossRefPubMedPubMedCentral

30.

McKenzie CGJ, Koser U, Lewis LE, Bain JM, Mora-Montes HM, Barker RN, et al. Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages. Infect Immun. 2010;78(4):1650–8. https://doi.org/10.1128/IAI.00001-10.CrossRefPubMedPubMedCentral

31.

Lohse MB, Gulati M, Johnson AD, Nobile CJ. Development and regulation of single-and multi-species Candida albicans biofilms. Nat Rev Microbiol. 2018;16(1):19–31. https://doi.org/10.1038/nrmicro.2017.107.CrossRefPubMed

32.

Nobile CJ, Johnson AD. Candida albicans biofilms and human disease. Annu Rev Microbiol. 2015;69(1):71–92. https://doi.org/10.1146/annurev-micro-091014-104330.CrossRefPubMedPubMedCentral

33.

Danielsson D, Teigen PK, Moi H. The genital econiche: focus on microbiota and bacterial vaginosis. Ann N Y Acad Sci. 2011;1230(1):48–58. https://doi.org/10.1111/j.1749-6632.2011.06041.x.CrossRefPubMed

34.

Joo HM, Kim KA, Myoung KS, Ahn YT, Lee JH, Huh CS, et al. Lactobacillus helveticus HY7801 ameliorates vulvovaginal candidiasis in mice by inhibiting fungal growth and NF-κB activation. Int Immunopharmacol. 2012;14(1):39–46. https://doi.org/10.1016/j.intimp.2012.05.023.CrossRefPubMed

35.

Falagas ME, Betsi GI, Athanasiou S. Probiotics for prevention of recurrent vulvovaginal candidiasis: a review. J Antimicrob Chemother. 2006;58(2):266–72. https://doi.org/10.1093/jac/dkl246.CrossRefPubMed

Title: Inhibitory effects of Lactobacillus casei Shirota against both Candida auris and Candida spp. isolates that cause vulvovaginal candidiasis and are resistant to antifungals
Authors: Aline Lorenzoni Paniágua
Amabel Fernandes Correia
Lívia Custódio Pereira
Bruna Maciel de Alencar
Fabiana Brandão Alves Silva
Rosane Mansan Almeida
Yanna Karla de Medeiros Nóbrega
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Vulvovaginal Candidiasis
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03405-z

Keynote webinar | Spotlight on medication adherence

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Inhibitory effects of Lactobacillus casei Shirota against both Candida auris and Candida spp. isolates that cause vulvovaginal candidiasis and are resistant to antifungals

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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