Correlation of antifungal susceptibility and sequence types within Cryptococcus neoformans VNI from HIV patients, and ERG11 gene polymorphism.

Bive, Bive Zono; Sacheli, Rosalie; Mudogo, Celestin Nzanzu; Zakayi, Pius Kabututu; Bontems, Sébastien; Lelo, Georges Mvumbi; Hayette, Marie-Pierre

doi:10.1016/j.mycmed.2023.101428

Article (Scientific journals)

Correlation of antifungal susceptibility and sequence types within Cryptococcus neoformans VNI from HIV patients, and ERG11 gene polymorphism.

Bive, Bive Zono; Sacheli, Rosalie; Mudogo, Celestin Nzanzu et al.

2023 • In Journal de Mycologie Médicale, 33 (4), p. 101428

Peer reviewed

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https://hdl.handle.net/2268/308034

DOI
10.1016/j.mycmed.2023.101428

PubMed
37651769

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Keywords :

Antifungal susceptibility; Cryptococcus neoformans; Democratic Republic of Congo; ERG11; EUCAST; Kinshasa; People living with HIV; Infectious Diseases

Abstract :

[en] [en] INTRODUCTION: Here we tested the correlation between minimum inhibitory concentrations (MICs) of major antifungal agents and sequence types (STs) within Cryptococcus neoformans VNI isolates, and explored the ERG11 gene of included strains. MATERIALS AND METHODS: We analysed 23 C. neoformans strains categorised into two groups according to the distribution of the ST profile in Kinshasa clinics (Democratic Republic of Congo): major ST [ST93 (n = 15)], and less common STs [ST659 (n = 2), ST5 (n = 2), ST4 (n = 1), ST 53 (n = 1), ST31 (n = 1), and ST69 (n = 1)]. The MICs of the major antifungal agents [amphotericin B (AMB), 5-fluorocytosine (5FC) and fluconazole (FCZ)] were determined following EUCAST guidelines. ERG11 gene sequences were extracted from whole genome sequence of the isolates and compared with the wild-type gene sequence of the C. neoformans VNI. RESULTS: Although major ST isolates appeared to have lower median MICs for AMB and 5FU than less common ST isolates (0.50 vs. 0.75 mg/L for AMB, 2 vs. 4 mg/L for 5FU, respectively), FCZ susceptibility was similar in both groups (4 mg/L) (p-value >0.05). The susceptibility profile of C. neoformans strains separately considered did not significantly affect the patients' clinical outcomes (p-value >0.05). Furthermore, two structural modalities of the ERG11 gene were observed: (1) that of the reference gene, and (2) that containing two exonic silent point substitutions, and one intronic point substitution located in a sequence potentially involved in pre-mRNA splicing (c.337-22C > T); with no association with the MICs of the isolates (p-value >0.05). CONCLUSIONS: The lack of association/correlation found in this study calls for further investigations to better understand the mechanisms of C. neoformans resistance to antifungal agents.

Disciplines :

Laboratory medicine & medical technology

Author, co-author :

Bive, Bive Zono ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo, Department of Clinical Microbiology, National Reference Center for Mycosis, Center for Interdisciplinary Research on Medicines, University of Liege, Liege, Belgium. Electronic address: bive.zono@unikin.ac.cd

Sacheli, Rosalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique

Mudogo, Celestin Nzanzu ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo

Zakayi, Pius Kabututu ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo

Bontems, Sébastien ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique

Lelo, Georges Mvumbi ; Molecular Biology Service, Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo

Hayette, Marie-Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique

Language :

English

Title :

Correlation of antifungal susceptibility and sequence types within Cryptococcus neoformans VNI from HIV patients, and ERG11 gene polymorphism.

Publication date :

25 August 2023

Journal title :

Journal de Mycologie Médicale

ISSN :

1156-5233

Publisher :

Elsevier Masson s.r.l., France

Volume :

Issue :

Pages :

101428

Peer reviewed :

Peer reviewed

Additional URL :

https://api.elsevier.com/content/article/PII:S1156523323000720?httpAccept=text/xml

Funding text :

We would like to thank the Académie de Recherche et d'Enseignement Supérieur (ARES-Belgium) for the support.

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since 21 October 2023

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Bibliography

Francisco, E.C., de Jong, A.W., Hagen, F., Cryptococcosis and Cryptococcus. Mycopathologia 186 (2021), 729–731, 10.1007/s11046-021-00577-7.
Hagen, F., Khayhan, K., Theelen, B., Kolecka, A., Polacheck, I., Sionov, E., Falk, R., Parnmen, S., Lumbsch, H.T., Boekhout, T., Recognition of seven species in the Cryptococcus gattii /Cryptococcus neoformans species complex. Fungal Genet Biol 78 (2015), 16–48, 10.1016/j.fgb.2015.02.009.
Meyer, W., Aanensen, D.M., Boekhout, T., Cogliati, M., Diaz, M.R., Esposto, M.C., Fisher, M., Gilgado, F., Hagen, F., Litvintseva, A.P., Mitchell, T.G., Simwami, S.P., Viviani, M.A., Kwon-chung, J., Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol 47 (2009), 561–570, 10.1080/13693780902953886.Consensus.
Rajasingham, R., Govender, N.P., Jordan, A., Loyse, A., Shroufi, A., Denning, D.W., Meya, D.B., Chiller, T.M., Boulware, D.R., The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis 3099 (2022), 1–8, 10.1016/s1473-3099(22)00499-6.
F. CDC, Ending cryptococcal meningitis deaths by 2030: strategic framework, 2021. https://dndi.org/wp-content/uploads/2021/05/End Cryptococcal Meningitis Deaths 2030-StrategicFramework-EN-2021.pdf.
World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. 2022, WHO, 48 https://www.who.int/publications/i/item/9789240052178.
Driemeyer, C., Falci, D.R., Oladele, R.O., Bongomin, F., Ocansey, B.K., Govender, N.P., Hoenigl, M., Gangneux, J.P., Meis, J.F., Bruns, C., Stemler, J., Pasqualotto, A.C., The current state of clinical mycology in Africa: a European Confederation of Medical Mycology and International Society for Human and Animal Mycology survey. Lancet Microbe 5247 (2022), 1–7, 10.1016/S2666-5247(21)00190-7.
Bongomin, F., Oladele, R.O., Gago, S., Moore, C.B., Richardson, M.D., A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species. Mycoses 61 (2018), 290–297, 10.1111/myc.12747.
Gago, S., Serrano, C., Alastruey-Izquierdo, A., Cuesta, I., Martín-Mazuelos, E., Aller, A.I., Gómez-López, A., Mellado, E., Molecular identification, antifungal resistance and virulence of Cryptococcus neoformans and Cryptococcus deneoformans isolated in Seville, Spain. Mycoses 60 (2017), 40–50, 10.1111/myc.12543.
Bii, C.C., Makimura, K., Abe, S., Taguchi, H., Mugasia, O.M., Revathi, G., Wamae, N.C., Kamiya, S., Antifungal drug susceptibility of Cryptococcus neoformans from clinical sources in Nairobi, Kenya. Mycoses Diagn, Ther Prophyl Fungal Dis 50 (2007), 25–30, 10.1111/j.1439-0507.2006.01293.x.
Kammalac Ngouana, T., Dongtsa, J., Kouanfack, C., Tonfack, C., Fomena, S., Mallié, M., Delaporte, E., Boyom, F.F., Bertout, S., Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole. J Mycol Med 25 (2015), 11–16, 10.1016/j.mycmed.2014.10.016.
Rodero, L., Mellado, E., Rodriguez, A.C., Salve, A., Guelfand, L., Cahn, P., Cuenca-Estrella, M., Davel, G., Rodriguez-Tudela, J.L., G484S amino acid substitution in lanosterol 14-α demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate. Antimicrob Agents Chemother 47 (2003), 3653–3656, 10.1128/AAC.47.11.3653-3656.2003.
Chang, M., Sionov, E., Lamichhane, A.K., Kwon-chung, K.J., Chang, Y.C., Roles of three Cryptococcus neoformans and Cryptococcus gattii efflux pump-coding genes in response to drug treatment. Antimicrob Agents Chemother 62 (2018), 1–14, 10.1128/AAC.01751-17.
Sanguinetti, M., Posteraro, B., La Sorda, M., Torelli, R., Fiori, B., Santangelo, R., Delogu, G., Fadda, G., Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans. Infect Immun 74 (2006), 1352–1359, 10.1128/IAI.74.2.1352-1359.2006.
Posteraro, B., Sanguinetti, M., Sanglard, D., La Sorda, M., Boccia, S., Romano, L., Morace, G., Fadda, G., Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol 47 (2003), 357–371, 10.1046/j.1365-2958.2003.03281.x.
Zono Bive, B., Kasumba, D.M., Situakibanza Nani-Tuma, H., Bepouka Izizag, B., Yambayamba Kapenga, M., Nsuka Yanga, R., Tshimanga Yona, T., Kamangu Ntambwe, E., Hayette, M., Mvumbi Lelo, G., Cryptococcosis in the Democratic Republic of Congo from 1953 to 2021: a systematic review and meta-analysis. Mycoses, 2022, 1–10, 10.1111/myc.13440.
Zono, B.B., Sacheli, R., Situakibanza, N.H., Kabututu, Z.P., Ka, A., Mbula, M.M., Muendele, G., Boreux, R., Landu, N., Mudogo, C.N., M'Buze, P.-R., Moutschen, M., Meyer, W., Mvumbi, L.G., Hayette, M.-P., Clinical epidemiology and high genetic diversity amongst Cryptococcus spp. isolates infecting people living with HIV in Kinshasa, Democratic Republic of Congo. PLoS One 17 (2022), 1–15, 10.1371/journal.pone.0267842.
S.A. Medecins Sans Frontières, Les négligés de l'infection au VIH Patients en stade VIH avancé: une prise en charge adaptée et gratuite est leur seule chance de survie, Ghizlaine, KInshasa, 2017. https://samumsf.org/sites/default/files/2017-08/MSFKinshasaReportdigital_0.pdf.
Trilles, L., Meyer, W., Wanke, B., Guarro, J., Lazéra, M., Correlation of antifungal susceptibility and molecular type within the Cryptococcus neoformans/C. gattii species complex. Med Mycol 50 (2012), 328–332, 10.3109/13693786.2011.602126.
EUCAST. Susceptibility testing of yeasts. Clin Microbiol Infect 3 (2017), 14–16, 10.1111/j.1469-0691.1997.tb00893.x.
M. CLSI, M59. Epidemiological Cut-off Values for Antifungal Susceptibility Testing., 2020.
Illumina, Nextera XT DNA Library Prep Kit, 2017.
Perfect, J.R., Cox, G.M., Drug resistance in Cryptococcus neoformans. Drug Resist Updat, 1999, 259–269, 10.1007/978-1-59745-180-2_41.
Iwata, K., Drug resistance in Human pathogenic fungi. Eur J Epidemiol 8 (1992), 407–421, 10.1007/BF00158576.
Cuenca-Estrella, M., Díaz-Guerra, T.M., Mellado, E., Rodríguez-Tudela, J.L., Flucytosine primary resistance in Candida species and Cryptococcus neoformans. Eur J Clin Microbiol Infect Dis 20 (2001), 276–279, 10.1007/PL00011265.
Schwarz, P., Lortholary, O., Dannaoui, E., Efficacy of amphotericin B in combination with flucytosine against flucytosine-susceptible or flucytosine-resistant isolates of Cryptococcus neoformans during disseminated murine cryptococcosis. Antimicrob Agents Chemother 50 (2006), 113–120, 10.1128/AAC.50.1.113.
Geddes-mcalister, A.B.J., Combatting the evolution of antifungal resistance in Cryptococcus neoformans. Microreview, 2020, 721–734, 10.1111/mmi.14565.
Ngouana, K., Dongtsa, J., Kouanfack, C., Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole. J Mycol Médicale 25 (2015), 11–16.
Alcazar-Fuoli, L., Mellado, E., Current status of antifungal resistance and its impact on clinical practice. Br J Haematol 166 (2014), 471–484, 10.1111/bjh.12896.
Morio, F., Loge, C., Besse, B., Hennequin, C., Pape, P.Le, Screening for amino acid substitutions in the Candida albicans ERG11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagn Microbiol Infect Dis 66 (2010), 373–384, 10.1016/j.diagmicrobio.2009.11.006.
Venkateswarlu, K., Taylor, M., Manning, N.J., Rinaldi, M.G., Kelly, S.L., Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother 41 (1997), 748–751, 10.1128/aac.41.4.748.
Sheng, C., Miao, Z., Ji, H., Yao, J., Wang, W., Che, X., Dong, G., Lü, J., Guo, W., Zhang, W., Three-dimensional model of lanosterol 14α-demethylase from Cryptococcus neoformans: active-site characterization and insights into azole binding. Antimicrob Agents Chemother 53 (2009), 3487–3495, 10.1128/AAC.01630-08.
Atim, P.B., Meya, D.B., Gerlach, E.S., Muhanguzi, D., Male, A., Kanamwanji, B., Nielsen, K., Lack of association between fluconazole susceptibility and ERG11 nucleotide polymorphisms in Cryptococcus neoformans clinical isolates from Uganda. J Fungi, 8, 2022, 508, 10.3390/jof8050508.
Ward, A.J., Cooper, T.A., The pathology of splicing. J Pathol 2010 (2009), 152–163, 10.1002/path.
Nembaware, V., Lupindo, B., Schouest, K., Spillane, C., Scheffler, K., Seoighe, C., Genome-wide survey of allele-specific splicing in humans. BMC Genom 9 (2008), 1–15, 10.1186/1471-2164-9-265.
Langford, C.J., Gallwitz, D., Evidence for an intron-contained sequence required for the splicing of yeast RNA polymerase II transcripts. Cell 33 (1983), 519–527, 10.1016/0092-8674(83)90433-6.
Newman, A.J., fang Lin, R., Cheng, S.C., Abelson, J., Molecular consequences of specific intron mutations on yeast mRNA splicing in vivo and in vitro. Cell 42 (1985), 335–344, 10.1016/S0092-8674(85)80129-X.