Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species
Abstract Pulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologic Aspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologic Aspergillus species which belonged to two major species, i.e., A. flavus and A. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression of cyp51A, Cdr1B, and Yap1 genes was analyzed in voriconazole-intermediate/resistant isolates. In A. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In the Yap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously in A. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes of A. fumigatus. The expression of Yap1 was higher than that of two other genes in both A. flavus and A. fumigatus. Overall, voriconazole-resistant strains of both A. fumigatus and A. flavus demonstrated overexpression of Cdr1B, Cyp51A, and Yap1 genes compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of resistant and intermediate isolates, while all of these isolates showed overexpression in all three genes studied. As a conclusion, it seems that the main reason of the emergence of mutation in voriconazole-resistant isolates of A. flavus and A. fumigatus is previous or prolonged exposure to azoles..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
|---|---|
| Enthalten in: |
European journal of clinical microbiology & infectious diseases - 42(2023), 7 vom: 05. Mai, Seite 853-864 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Salehi, Zahra [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| Themen: |
Antifungal susceptibility |
|---|
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
|---|
| doi: |
10.1007/s10096-023-04608-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2143859635 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2143859635 | ||
| 003 | DE-627 | ||
| 005 | 20240118092119.0 | ||
| 007 | tu | ||
| 008 | 240118s2023 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s10096-023-04608-7 |2 doi | |
| 035 | |a (DE-627)OLC2143859635 | ||
| 035 | |a (DE-He213)s10096-023-04608-7-p | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |a 570 |q VZ |
| 082 | 0 | 4 | |a 610 |q VZ |
| 100 | 1 | |a Salehi, Zahra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical epidemiology of pulmonary aspergillosis in hospitalized patients and contribution of Cyp51A, Yap1, and Cdr1B mutations to voriconazole resistance in etiologic Aspergillus species |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. | ||
| 520 | |a Abstract Pulmonary aspergillosis is a life-threatening fungal infection with worldwide distribution. In the present study, clinical epidemiology of pulmonary aspergillosis and antifungal susceptibility of etiologic Aspergillus species were evaluated in one-hundred fifty patients with special focus on the frequency of voriconazole resistance. All the cases were confirmed by the clinical pictures, laboratory findings, and isolation of etiologic Aspergillus species which belonged to two major species, i.e., A. flavus and A. fumigatus. Seventeen isolates displayed voriconazole MIC greater than or equal to the epidemiological cutoff value. Expression of cyp51A, Cdr1B, and Yap1 genes was analyzed in voriconazole-intermediate/resistant isolates. In A. flavus, Cyp51A protein sequencing showed the substitutions T335A and D282E. In the Yap1 gene, A78C replacement led to Q26H amino acid substitution that was not reported previously in A. flavus resistant to voriconazole. No mutations associated with voriconazole resistance were found in the three genes of A. fumigatus. The expression of Yap1 was higher than that of two other genes in both A. flavus and A. fumigatus. Overall, voriconazole-resistant strains of both A. fumigatus and A. flavus demonstrated overexpression of Cdr1B, Cyp51A, and Yap1 genes compared to voriconazole-susceptible strains. Although there are still ambiguous points about the mechanisms of azole resistance, our results showed that mutations were not present in majority of resistant and intermediate isolates, while all of these isolates showed overexpression in all three genes studied. As a conclusion, it seems that the main reason of the emergence of mutation in voriconazole-resistant isolates of A. flavus and A. fumigatus is previous or prolonged exposure to azoles. | ||
| 650 | 4 | |a Pulmonary aspergillosis | |
| 650 | 4 | |a species | |
| 650 | 4 | |a Gene mutation | |
| 650 | 4 | |a Overexpression | |
| 650 | 4 | |a Antifungal susceptibility | |
| 650 | 4 | |a Voriconazole resistance | |
| 700 | 1 | |a Sharifynia, Somayeh |4 aut | |
| 700 | 1 | |a Jamzivar, Fatemehsadat |4 aut | |
| 700 | 1 | |a Shams-Ghahfarokhi, Masoomeh |4 aut | |
| 700 | 1 | |a Poorabdollah, Mihan |4 aut | |
| 700 | 1 | |a Abtahian, Zahra |4 aut | |
| 700 | 1 | |a Nasiri, Naser |4 aut | |
| 700 | 1 | |a Marjani, Majid |4 aut | |
| 700 | 1 | |a Moniri, Afshin |4 aut | |
| 700 | 1 | |a Salehi, Mohammadreza |4 aut | |
| 700 | 1 | |a Tabarsi, Payam |4 aut | |
| 700 | 1 | |a Razzaghi-Abyaneh, Mehdi |0 (orcid)0000-0001-8217-399X |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of clinical microbiology & infectious diseases |d Springer Berlin Heidelberg, 1982 |g 42(2023), 7 vom: 05. Mai, Seite 853-864 |w (DE-627)130396974 |w (DE-600)603155-9 |w (DE-576)015899780 |x 0934-9723 |7 nnns |
| 773 | 1 | 8 | |g volume:42 |g year:2023 |g number:7 |g day:05 |g month:05 |g pages:853-864 |
| 856 | 4 | 1 | |u https://doi.org/10.1007/s10096-023-04608-7 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a GBV_ILN_267 | ||
| 912 | |a GBV_ILN_2018 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4277 | ||
| 951 | |a AR | ||
| 952 | |d 42 |j 2023 |e 7 |b 05 |c 05 |h 853-864 | ||