Keywords
Histoplasmosis
Phenotypic Variation
Antigens
Antiretroviral Therapy
How to Cite
Abstract
Histoplasma capsulatum causes systemic mycosis that depends on host susceptibility, fungal virulence, and factors associated with the infectious process. We evaluated the possible interference of the phenotype of 12 samples of H. capsulatum isolated from HIV-positive and negative patients in obtaining antigens, aiming at the serological diagnosis through the gender-specific recognition of the H and M fractions. The antigens were evaluated by double immunodiffusion against H. capsulatum anti-antigen polyclonal antibody and serum samples from patients with histoplasmosis. The phenotypic evaluation revealed differences in the identification of the fungal agent and in the expression of H and M antigens, considered serological markers of the disease, associated with pigmentation and the production of conidia. It was found that antigenic preparations obtained from H. capsulatum isolated from HIV-positive patients may have satisfactory antigenic capacity. The patient’s immune status does not seem to interfere with the expression of antigenic proteins secreted by H. capsulatum. However, we suggest that prolonged use of antiretrovirals drugs or steroids can cause important phenotypic alterations. We showed that some fungal samples from patients with a long history of immunosuppressive drugs produced atypical cellular elements and low reactivity against the H and M fractions.
References
1. Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C. Histoplasmosis. Infect Dis Clin North Am. 2016;30(1):207-27. https://doi.org/10.1016/j.idc.2015.10.009
2 Azar MM, Loyd JL, Relich RF, Wheat LJ, Hage CA. Current concepts in the epidemiology, diagnosis, and management of histoplasmosis syndromes. Semin Respir Crit Care Med. 2020;41(1):13-30. https://doi.org/10.1055/s-0039-1698429
3 Sahaza JH, Pérez-Torres A, Zenteno E, Taylor ML. Usefulness of the murine model to study the immune response against Histoplasma capsulatum infection. Comp Immunol Microbiol Infect Dis. 2014;37(3):143-52. https://doi.org/10.1016/j.cimid.2014.03.002
4 Armstrong-James D, Meintjes G, Brown GD. A neglected epidemic: Fungal infections in HIV/AIDS. Trends Microbiol. 2014;22(3):120-7. http://dx.doi.org/10.1016/j.tim.2014.01.001
5 Almeida MA, Almeida-Silva F, Guimarães AJ, Almeida-Paes R, Zancopé-Oliveira RM. The occurrence of histoplasmosis in Brazil: A systematic review. Int J Infect Dis. 2019;86:147-56. https://doi.org/10.1016/j.ijid.2019.07.009
6 Adenis AA, Aznar C, Couppié P. Histoplasmosis in HIV-infected patients: A review of new developments and remaining gaps. Curr Trop Med Rep. 2014;1:119-28. https://doi.org/10.1007/s40475-014-0017-8
7 Franklin AD, Larson L, Rauseo AM, Rutjanawech S, Hendrix MJ, Powderly WG et al. A comparison of presentations and outcomes of histoplasmosis across patients with varying immune status. Med Mycol. 2021;59(6):624-33. https://doi.org/10.1093/mmy/myaa112
8 Arango-Bustamante K, Restrepo A, Cano LE, Bedout C, Tobón AM, González A. Diagnostic value of culture and serological tests in the diagnosis of histoplasmosis in HIV and non-HIV Colombian patients. Am J Trop Med Hyg. 2013;89(5):937-42. https://doi.org/10.4269/ajtmh.13-0117
9 Azar MM, Hage CA. Laboratory diagnostics for histoplasmosis. J Clin Microbiol. 201;55(6):1612-20. https://doi.org/10.1128/JCM.02430-16
10 Caceres DH, Chiller T, Lindsley MD. Immunodiagnostic assays for the investigation of fungal outbreaks. Mycopathologia. 2020;185(5):867-80. https://doi.org/10.1007/s11046-020-00452-x
11 Toscanini MA, Nusblat AD, Cuestas ML. Diagnosis of histoplasmosis: current status and perspectives. Appl Microbiol Biotechnol. 2021;105:1837-59. https://doi.org/10.1007/s00253-021-11170-9
12 Kaufman L, Standard P. Improved version of the exoantigen test for identification of Coccidioides immitis and Histoplasma capsulatum cultures. J Clin Microbiol. 1978;8(1):42-5. https://doi.org/10.1128/jcm.8.1.42-45.1978
13 Kaufman L, Standard P. Immuno-identification of cultures of fungi pathogenic to man. Curr Microbiol. 1978:1:135-40. https://doi.org/10.1007/BF02601665
14 Dantas KC, Freitas RS, Silva MV, Criado PR, Luiz OC, Vicentini AP. Comparison of diagnostic methods to detect Histoplasma capsulatum in serum and blood samples from AIDS patients. PLoS One. 2018;13(1):e0190408. https://doi.org/10.1371/journal.pone.0190408
15 Riddell RW. Permanent stained mycological preparations obtained by slide culture. Mycologia. 1950;42(2):265-70. https://doi.org/10.2307/3755439
16 Freitas RS, Kamikawa CM, Vicentini AP. Fast protocol for the production of Histoplasma capsulatum antigens for antibody detection in the immunodiagnosis of histoplasmosis. Rev Iberoam Micol. 2018:35(1):27-31. https://doi.org/10.1016/j.riam.2017.04.004
17 Freitas RS, Carvalho-Vivi JO, Zamboni IM, Assis CM, Costa-Martins JE, Vicentini-Moreira AP. The importance of serological assays in diagnosing acute pulmonary histoplasmosis. J Venom Anim Toxins Incl Trop Dis. 2009;15(2):278-88. https://doi.org/10.1590/S167891992009000200010
18 Mckinney MM, Parkinson A. A simple non-chromatographic procedureto purify immunoglobulins from serum and ascites fluids. J immunol Meth. 1987;96(2):271-8. https://doi.org/10.1016/0022-1759(87)90324-3
19. Hussain K, Malavia D, Johnson EM, Littlechild J, Winlove CP, Vollmer F et al. Biosensors and diagnostics for fungal detection. J Fungi. 2020;6(4):349. https://doi.org/10.3390/jof6040349
20 Domer JE. Monosaccharide and chitin content of cell walls of Histoplasma capsulatum and Blastomyces dermatitidis. J Bacteriol. 1971;107(3):870-7. https://doi.org/10.1128/jb.107.3.870-877.1971
21 Gorocica P, Taylor ML, Alvarado-Vásquez N, Pérez-Torres A, Lascurain R, Zenteno E. The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis. Mem Inst Oswaldo Cruz. 2009;104(3):492-6. https://doi.org/10.1590/s0074-02762009000300016
22 Kanetsuna F, Carbonell LM, Azuma I, Yamamura Y. Biochemical studies on the thermal dimorphism of Paracoccidioides brasiliensis. J Bacteriol. 1972;110(1):208-18. https://doi.org/10.1128/jb.110.1.208-218.1972
23 Kanetsuna F, Carbonell LM, Gil F, Azuma I. Chemical and ultrastructural studies on the cell walls of the yeast like and mycelial forms of Histoplasma capsulatum. Mycopathol Mycol Appl. 1974;54(1):1-13. https://doi.org/10.1007/BF02055967
24 Kanetsuna F. Ultrastructural studies on the dimorphism of Paracoccidioides brasiliensis, Blastomyces dermatitidis and Histoplasma capsulatum Sabouraudia. 1981;19(4):275-86. https://doi.org/10.1080/00362178185380451
25 Klimpel KR, Goldman WE. Cell walls from avirulent variants of Histoplasma capsulatum lack alpha-(1,3)-glucan. Infect Immun. 1988;56(11):2997-3000. https://doi.org/10.1128/iai.56.11.2997-3000.1988
26 Rappleye CA, Engle JT, Goldman WE. RNA interference in Histoplasma capsulatum demonstrates a role for α-(1,3)-glucan in virulence. Mol Microbiol. 2004;53(1):153-65. https://doi.org/10.1111/j.1365-2958.2004.04131.x
27 Ehrhard HB, Pine L. Factor influencing the production of H and M antigens by Histoplasma capsulatum: Development and evaluation of shake culture procedure. Appl Microbiol. 1972;23(2):236-49. https://doi.org/10.1128/am.23.2.236-249.1972
28 Berliner MD. Primary subcultures of Histoplasma capsulatum: I. Macro and micromorphology of the mycelial phase. Sabouraudia. 1968;6(2):111-8. https://doi.org/10.1080/00362176885190211
29 Borok R. The mycelial status and reversibility in Histoplasma capsulatum. Sabouraudia. 1980;18(4):249-53. https://doi.org/10.1080/00362178085380431
30 Freitas RS, Neves PS, Charbel CE, Criado PR, Nunes RS, Santos-Filho AM et al. Investigation of superficial mycosis in cutaneous allergy patients using topical or systemic corticosteroids. Int J Dermatol. 2017;56(10):e194-e198. https://doi.org/10.1111/ijd.13651
31 Cresnar B, Zakelj-Mavric M. Aspects of the steroid response in fungi. Chem Biol Interact. 2009;178(1-3):303-9. https://doi.org/10.1016/j.cbi.2008.11.002
32 Ledtke C, Rehm SJ, Fraser TG, Shrestha NK, Tan CD, Rodriguez ER et al. Endovascular infections caused by Histoplasma capsulatum: A case series and review of the literature. Arch Pathol Lab. 2012;136(6):640-5. https://doi.org/10.5858/arpa.2011-0050-OA
33 Damasceno LS, Teixeira MM, Barker BM, Almeida MA, Muniz MM, Pizzini CV et al. Novel clinical and dual infection by Histoplasma capsulatum genotypes in HIV patients from Northeastern, Brazil. Sci Rep. 2019;9:11789. https://doi.org/10.1038/s41598-019-48111-6
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 1969 Roseli Santos de Freitas-Xavier, Isabel Alves Feitosa Maciel, Vera Lúcia Teixeira de Freitas, Adriana Pardini Vicentini