Molecular characterization and improved diagnostics of Nocardia strains isolated over the last two decades at a German tertiary care center

Authors

  • Patrick Chhatwal Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, Gebäude J6, 30625 Hannover, Germany. E-mail: chhatwal.patrick@mh-hannover.de https://orcid.org/0000-0001-9957-8571
  • Sabrina Woltemate Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany
  • Stefan Ziesing Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany
  • Tobias Welte Department of Pneumology and German Center for Lung Research, Hannover Medical School (MHH), Hannover, Germany
  • Dirk Schlüter Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany https://orcid.org/0000-0003-1478-3328
  • Marius Vital Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, Gebäude J6, 30625 Hannover, Germany. E-mail: vital.marius@mh-hannover.de https://orcid.org/0000-0003-4185-3475

DOI:

https://doi.org/10.17179/excli2021-3787

Keywords:

Nocardia, whole genome sequencing, resistance mechanisms, molecular diagnostics, transplantation

Abstract

Nocardiosis is a rare but life-threatening infection caused by aerobic Actinomycetes of the genus Nocardia particularly affecting immunocompromised hosts. The identification of Nocardia ssp. and antibiotic susceptibility testing by standard microbiological methods are incomplete and molecular techniques may improve diagnostics. We studied 39 Nocardia strains isolated from 33 patients between 2000 and 2018. Twenty-four patients (72.7 %) were immunocompromised. Whole genome sequencing (WGS) revealed a broad taxonomic range of those isolates spanning 13 different species, including four strains that belonged to three novel species based on average nucleotide identity (ANI < 95 % with currently available genome sequences). 16S rRNA gene analyses mirrored WGS results. Conventional MALDI-TOF analysis correctly identified 29 isolates at the species level (74.4 %). Our advanced protocol with formic acid and acetonitrile treatment increased identification to 35 isolates (89.7 %). Antibiotic resistance was tested using both a microdilution method and MIC strip testing. Results were in good concordance with an overall trimethoprim-sulfamethoxazole (SXT) resistance rate of 13.5 %. WGS of a SXT resistant N. farcinica isolate showed a deletion of several amino acids in a homolog of dihydropteroate synthase (FolP2) that was not seen in sensitive members of this species. Diversity of Nocardia isolates was high and involved many different species, suggesting that this taxon has broadly distributed mechanisms for infecting individuals. Widely applicable diagnostic methods including MALDI-TOF and 16S rRNA gene analyses correctly identified most strains. WGS additionally revealed molecular insights into SXT resistance mechanisms of clinical Nocardia isolates highlighting the potential application of (meta)genomic-based diagnostics in the future.

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Published

2021-04-30

How to Cite

Chhatwal, P., Woltemate, S., Ziesing, S., Welte, T., Schlüter, D., & Vital, M. (2021). Molecular characterization and improved diagnostics of Nocardia strains isolated over the last two decades at a German tertiary care center. EXCLI Journal, 20, 851–862. https://doi.org/10.17179/excli2021-3787

Issue

Vol. 20 (2021)

Section

Original articles

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Copyright (c) 2021 Patrick Chhatwal, Sabrina Woltemate, Stefan Ziesing, Tobias Welte, Dirk Schlüter, Marius Vital

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