Genetic diversity of clinical and environmental Mucorales isolates obtained from an investigation of mucormycosis cases among solid organ transplant recipients

Abstract

Mucormycoses are invasive infections by Rhizopus species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to Rhizopus microsporus (n=2), R. arrhizus (n=1) or Lichtheimia corymbifera (n=1), at a median 31.5 days (range: 13–34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 R. arrhizus, 19 R. delemar, six R. microsporus, two Lichtheimia species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine–cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of R. microsporus isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.

Phenotypic analysis and genome sequence of Rhizopus oryzae strain Y5, the causal agent of tobacco pole rot

“…Reference sequences ( Supplementary Table S1 ) from Nguyen et al (2020) were downloaded from GenBank, the evolutionary history was inferred using the Neighbor-Joining method ( Saitou and Nei, 1987 ), evolutionary analyses were conducted in MEGA7 ( Kumar et al, 2016 ).…”

“…Genomic data are a useful resource to understand the mechanism of plant-pathogen interaction and are used in the phylogenetic analyses of the species ( Ailloud et al, 2015 ). Beyond the isolate of R. oryzae from tobacco, many strains of R. oryzae were isolated from sweet potato, mulberry, lily ( Holmes et al, 2002 ) and the human body ( Nguyen et al, 2020 ). Information obtained from the National Center for Biotechnology Information (NCBI) could be learned that a total of 43 strains of R. oryzae had been sequenced, and there were less differences of genomic data with different R. oryzae strains.…”

Within-Host Genotypic and Phenotypic Diversity of Contemporaneous Carbapenem-Resistant Klebsiella pneumoniae from Blood Cultures of Patients with Bacteremia

“…At present, our findings and those of studies showing bacterial genetic diversity at nonbloodstream sites have important implications for molecular epidemiologic investigations of infectious outbreaks and nosocomial transmission of pathogens. Data here and in our previous study of clinical and environmental Mucorales suggest caution in relying upon core genome SNP phylogeny as the sole tool in defining differences between strains ( 45 ). In both studies, comprehensive pan-genome analyses revealed variations that were not apparent with core genome SNP comparisons.…”

Within-host genotypic and phenotypic diversity of contemporaneous carbapenem-resistant Klebsiella pneumoniae from blood cultures of patients with bacteremia

“…At present, our findings and those of studies showing bacterial genetic diversity at non-bloodstream sites have important implications for molecular epidemiologic investigations of infectious outbreaks and nosocomial transmission of pathogens. Data here and in our previous study of clinical and environmental Mucorales suggest caution in relying upon core genome SNP phylogeny as the sole tool in defining differences between strains (44). In both studies, comprehensive pan-genome analyses revealed variations that were not apparent with core genome comparisons.…”