Genomic Insights into Diversity: The Genome of Two Clinical Isolates and Their Demethylase Inhibitor Fungicides Susceptibility

Overview

Journal Pathogens

Date 2025 Jan 8

PMID 39770322

Authors

Luca Degradi

Valeria Tava

Maria Carmela Esposto

Anna Prigitano

Daniela Bulgari

Andrea Kunova

Marco Saracchi

Paolo Cortesi

Matias Pasquali

Affiliations

Soon will be listed here.

Abstract

is an important plant pathogen in maize and other cereals that is seldom detected as the cause of human fusariosis. Here, we provide the analysis of the available diversity of sequenced worldwide and report the first two genome assemblies and annotations (including mitochondrial DNA) of from clinical settings. 05-0160 (IUM05-0160) and 09-1037 (IUM09-1037) strains were obtained from the bone marrow and blood of two immunocompromised patients, respectively. The phylogenomic analysis confirmed the species identity of our two strains. Comparative genomic analyses among the reannotated genomes ( = 46) did not lead to the identification of unique genes specific to the clinical samples. Two subgroups in the clade were also identified and confirmed by a mitochondrial diversity study. Clinical strains ( = 4) were positioned in the multigene phylogenetic tree without any correlation between the host and the tree branches, grouping with plant-derived strains. To investigate the existence of a potential fitness advantage of our two clinical strains, we compared demethylase inhibitor fungicides susceptibility against the reference 7600, showing, on average, lower susceptibility to agricultural and medical-used antifungals. A significant reduction in susceptibility was observed for itraconazole and tetraconazole, which might be explained by structural changes in CYP51A and CYP51C sequences. By providing the first two annotated genomes of from clinical settings comprehensive of their mitogenomes, this study can serve as a base for exploring the fitness and adaptation capacities of infecting different kingdoms.

References

Shapiro R, Robbins N, Cowen L . Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev. 2011; 75(2):213-67. PMC: 3122626. DOI: 10.1128/MMBR.00045-10. View

Tupaki-Sreepurna A, Thanneru V, Natarajan S, Sharma S, Gopi A, Sundaram M . Phylogenetic Diversity and In Vitro Susceptibility Profiles of Human Pathogenic Members of the Fusarium fujikuroi Species Complex Isolated from South India. Mycopathologia. 2018; 183(3):529-540. DOI: 10.1007/s11046-018-0248-7. View

Mochizuki K, Shiraki I, Murase H, Ohkusu K, Nishimura K . Identification and sensitivity of two rare fungal species isolated from two patients with Fusarium keratomycosis. J Infect Chemother. 2012; 18(6):939-44. DOI: 10.1007/s10156-012-0389-4. View

Castro Lopez N, Casas C, Sopo L, Rojas A, Del Portillo P, de Garcia M . Fusarium species detected in onychomycosis in Colombia. Mycoses. 2008; 52(4):350-6. DOI: 10.1111/j.1439-0507.2008.01619.x. View

Al-Reedy R, Malireddy R, Dillman C, Kennell J . Comparative analysis of Fusarium mitochondrial genomes reveals a highly variable region that encodes an exceptionally large open reading frame. Fungal Genet Biol. 2011; 49(1):2-14. DOI: 10.1016/j.fgb.2011.11.008. View

Zhu G, Fu M, Zhang Y, Lu L . A ubiquitin-mediated post-translational degradation of Cyp51A contributes to a novel azole resistance mode in Aspergillus fumigatus. Microbiol Res. 2024; 289:127891. DOI: 10.1016/j.micres.2024.127891. View

Lockhart S, Chowdhary A, Gold J . The rapid emergence of antifungal-resistant human-pathogenic fungi. Nat Rev Microbiol. 2023; 21(12):818-832. PMC: 10859884. DOI: 10.1038/s41579-023-00960-9. View

Tortorano A, Prigitano A, Dho G, Esposto M, Gianni C, Grancini A . Species distribution and in vitro antifungal susceptibility patterns of 75 clinical isolates of Fusarium spp. from northern Italy. Antimicrob Agents Chemother. 2008; 52(7):2683-5. PMC: 2443921. DOI: 10.1128/AAC.00272-08. View

Mullins J, Parker J, Cools H, Togawa R, Lucas J, Fraaije B . Molecular modelling of the emergence of azole resistance in Mycosphaerella graminicola. PLoS One. 2011; 6(6):e20973. PMC: 3124474. DOI: 10.1371/journal.pone.0020973. View

10.

Navale V, Sawant A, Gowda V, Vamkudoth K . Assembly, Annotation, and Comparative Whole Genome Sequence of Isolated from Stored Maize Grains. Pathogens. 2022; 11(7). PMC: 9320718. DOI: 10.3390/pathogens11070810. View

11.

Mao C, Luo J, Zhang Y, Zhang C . Targeted deletion of three CYP51s in Fusarium fujikuroi and their different roles in determining sensitivity to 14α-demethylase inhibitor fungicides. Pest Manag Sci. 2022; 79(4):1324-1330. DOI: 10.1002/ps.7304. View

12.

Snelders E, Karawajczyk A, Schaftenaar G, Verweij P, Melchers W . Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling. Antimicrob Agents Chemother. 2010; 54(6):2425-30. PMC: 2876375. DOI: 10.1128/AAC.01599-09. View

13.

Brown G, Ballou E, Bates S, Bignell E, Borman A, Brand A . The pathobiology of human fungal infections. Nat Rev Microbiol. 2024; 22(11):687-704. DOI: 10.1038/s41579-024-01062-w. View

14.

Burger G, Yan Y, Javadi P, Lang B . Group I-intron trans-splicing and mRNA editing in the mitochondria of placozoan animals. Trends Genet. 2009; 25(9):381-6. DOI: 10.1016/j.tig.2009.07.003. View

15.

Macedo D, Neves R, Fontan J, Souza-Motta C, Lima D . A case of invasive rhinosinusitis by Fusarium verticillioides (Saccardo) Nirenberg in an apparently immunocompetent patient. Med Mycol. 2008; 46(5):499-503. DOI: 10.1080/13693780701861462. View

16.

Cocchi S, Codeluppi M, Venturelli C, Bedini A, Grottola A, Gennari W . Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole. Diagn Microbiol Infect Dis. 2011; 71(4):438-41. DOI: 10.1016/j.diagmicrobio.2011.08.024. View

17.

Fisher M, Henk D, Briggs C, Brownstein J, Madoff L, McCraw S . Emerging fungal threats to animal, plant and ecosystem health. Nature. 2012; 484(7393):186-94. PMC: 3821985. DOI: 10.1038/nature10947. View

18.

Twaruzek M, Soszczynska E, Winiarski P, Zwierz A, Grajewski J . The occurrence of molds in patients with chronic sinusitis. Eur Arch Otorhinolaryngol. 2013; 271(5):1143-8. DOI: 10.1007/s00405-013-2737-0. View

19.

Lucio J, Gonzalez-Jimenez I, Rivero-Menendez O, Alastruey-Izquierdo A, Pelaez T, Alcazar-Fuoli L . Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in . Genes (Basel). 2020; 11(10). PMC: 7602989. DOI: 10.3390/genes11101217. View

20.

Degradi L, Tava V, Prigitano A, Esposto M, Tortorano A, Saracchi M . Exploring Mitogenomes Diversity of from Banana Fruits and Human Patients. Microorganisms. 2022; 10(6). PMC: 9227538. DOI: 10.3390/microorganisms10061115. View