Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic
IntroductionMucormycosis is an acute invasive fungal disease (IFD) seen mainly in immunocompromised hosts and in patients with uncontrolled diabetes. The incidence of mucormycosis increased exponentially in India during the SARS-CoV-2 (henceforth COVID-19) pandemic. Since there was a lack of data on...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1251456/full |
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| author | Joy Sarojini Michael Manigandan Venkatesan Marilyn Mary Ninan Dhanalakshmi Solaimalai Lydia Jennifer Sumanth Lalee Varghese Regi Kurien Rinku Polachirakkal Varghese George Priya Doss C |
| author_facet | Joy Sarojini Michael Manigandan Venkatesan Marilyn Mary Ninan Dhanalakshmi Solaimalai Lydia Jennifer Sumanth Lalee Varghese Regi Kurien Rinku Polachirakkal Varghese George Priya Doss C |
| author_sort | Joy Sarojini Michael |
| collection | DOAJ |
| description | IntroductionMucormycosis is an acute invasive fungal disease (IFD) seen mainly in immunocompromised hosts and in patients with uncontrolled diabetes. The incidence of mucormycosis increased exponentially in India during the SARS-CoV-2 (henceforth COVID-19) pandemic. Since there was a lack of data on molecular epidemiology of Mucorales causing IFD during and after the COVID-19 pandemic, whole genome analysis of the Rhizopus spp. isolated during this period was studied along with the detection of mutations that are associated with antifungal drug resistance.Materials and methodsA total of 50 isolates of Rhizopus spp. were included in this prospective study, which included 28 from patients with active COVID-19 disease, 9 from patients during the recovery phase, and 13 isolates from COVID-19-negative patients. Whole genome sequencing (WGS) was performed for the isolates, and the de novo assembly was done with the Spades assembler. Species identification was done by extracting the ITS gene sequence from each isolate followed by searching Nucleotide BLAST. The phylogenetic trees were made with extracted ITS gene sequences and 12 eukaryotic core marker gene sequences, respectively, to assess the genetic distance between our isolates. Mutations associated with intrinsic drug resistance to fluconazole and voriconazole were analyzed.ResultsAll 50 patients presented to the hospital with acute fungal rhinosinusitis. These patients had a mean HbA1c of 11.2%, and a serum ferritin of 546.8 ng/mL. Twenty-five patients had received steroids. By WGS analysis, 62% of the Rhizopus species were identified as R. delemar. Bayesian analysis of population structure (BAPS) clustering categorized these isolates into five different groups, of which 28 belong to group 3, 9 to group 5, and 8 to group 1. Mutational analysis revealed that in the CYP51A gene, 50% of our isolates had frameshift mutations along with 7 synonymous mutations and 46% had only synonymous mutations, whereas in the CYP51B gene, 68% had only synonymous mutations and 26% did not have any mutations.ConclusionWGS analysis of Mucorales identified during and after the COVID-19 pandemic gives insight into the molecular epidemiology of these isolates in our community and establishes newer mechanisms for intrinsic azole resistance. |
| first_indexed | 2024-03-11T14:29:22Z |
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| last_indexed | 2024-03-11T14:29:22Z |
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| spelling | doaj.art-a098231a72af4f6ea2715ba58b4b4e902023-10-31T10:54:24ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-10-011310.3389/fcimb.2023.12514561251456Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemicJoy Sarojini Michael0Manigandan Venkatesan1Marilyn Mary Ninan2Dhanalakshmi Solaimalai3Lydia Jennifer Sumanth4Lalee Varghese5Regi Kurien6Rinku Polachirakkal Varghese7George Priya Doss C8Department of Clinical Microbiology, Christian Medical College, Vellore, Vellore, Tamil Nadu, IndiaDepartment of Clinical Microbiology, Christian Medical College, Vellore, Vellore, Tamil Nadu, IndiaDepartment of Clinical Microbiology, Christian Medical College, Vellore, Vellore, Tamil Nadu, IndiaDepartment of Clinical Microbiology, Christian Medical College, Vellore, Vellore, Tamil Nadu, IndiaDepartment of Clinical Microbiology, Christian Medical College, Vellore, Vellore, Tamil Nadu, IndiaDepartment of Otorhinolaryngology, Christian Medical College, Vellore, Vellore, IndiaDepartment of Otorhinolaryngology, Christian Medical College, Vellore, Vellore, IndiaDepartment of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT) University, Vellore, Tamil Nadu, IndiaDepartment of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT) University, Vellore, Tamil Nadu, IndiaIntroductionMucormycosis is an acute invasive fungal disease (IFD) seen mainly in immunocompromised hosts and in patients with uncontrolled diabetes. The incidence of mucormycosis increased exponentially in India during the SARS-CoV-2 (henceforth COVID-19) pandemic. Since there was a lack of data on molecular epidemiology of Mucorales causing IFD during and after the COVID-19 pandemic, whole genome analysis of the Rhizopus spp. isolated during this period was studied along with the detection of mutations that are associated with antifungal drug resistance.Materials and methodsA total of 50 isolates of Rhizopus spp. were included in this prospective study, which included 28 from patients with active COVID-19 disease, 9 from patients during the recovery phase, and 13 isolates from COVID-19-negative patients. Whole genome sequencing (WGS) was performed for the isolates, and the de novo assembly was done with the Spades assembler. Species identification was done by extracting the ITS gene sequence from each isolate followed by searching Nucleotide BLAST. The phylogenetic trees were made with extracted ITS gene sequences and 12 eukaryotic core marker gene sequences, respectively, to assess the genetic distance between our isolates. Mutations associated with intrinsic drug resistance to fluconazole and voriconazole were analyzed.ResultsAll 50 patients presented to the hospital with acute fungal rhinosinusitis. These patients had a mean HbA1c of 11.2%, and a serum ferritin of 546.8 ng/mL. Twenty-five patients had received steroids. By WGS analysis, 62% of the Rhizopus species were identified as R. delemar. Bayesian analysis of population structure (BAPS) clustering categorized these isolates into five different groups, of which 28 belong to group 3, 9 to group 5, and 8 to group 1. Mutational analysis revealed that in the CYP51A gene, 50% of our isolates had frameshift mutations along with 7 synonymous mutations and 46% had only synonymous mutations, whereas in the CYP51B gene, 68% had only synonymous mutations and 26% did not have any mutations.ConclusionWGS analysis of Mucorales identified during and after the COVID-19 pandemic gives insight into the molecular epidemiology of these isolates in our community and establishes newer mechanisms for intrinsic azole resistance.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1251456/fullwhole genome sequencingmolecular epidemiologyMucoralesCOVID - 19azole resistance detection |
| spellingShingle | Joy Sarojini Michael Manigandan Venkatesan Marilyn Mary Ninan Dhanalakshmi Solaimalai Lydia Jennifer Sumanth Lalee Varghese Regi Kurien Rinku Polachirakkal Varghese George Priya Doss C Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic Frontiers in Cellular and Infection Microbiology whole genome sequencing molecular epidemiology Mucorales COVID - 19 azole resistance detection |
| title | Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic |
| title_full | Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic |
| title_fullStr | Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic |
| title_full_unstemmed | Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic |
| title_short | Whole genome analysis of Rhizopus species causing rhino-cerebral mucormycosis during the COVID-19 pandemic |
| title_sort | whole genome analysis of rhizopus species causing rhino cerebral mucormycosis during the covid 19 pandemic |
| topic | whole genome sequencing molecular epidemiology Mucorales COVID - 19 azole resistance detection |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1251456/full |
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