Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing

Abstract

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.

A Revised Species Concept for OpportunisticMucorSpecies Reveals Species-Specific Antifungal Susceptibility Profiles

“…In Table S1 in the supplemental material) were studied belonging to three different families: (1) Mucoraceae: (13), M. racemosus f. racemosus (4), M. ramosissimus (1), M. variicolumellatus (2), and M. velutinosus (7); (ii) Rhizopodaceae: Rhizopus arrhizus (6) and R. microsporus (6); and (iii) Lichtheimiaceae: Lichtheimia corymbifera (8), L. ramosa (2), and Rhizomucor pusillus (5). Strains originated from clinical or environmental sources (Table S1).…”

The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains

“…Pathogenic fungi are known to spread rapidly worldwide facilitating fast evolution by introgressive hybridization and intragenic recombination amongst lineages in the plant pathogenic ascomycete Fusarium graminearum (O'Donnell et al ., ). Equally rapidly spreading pathogenicity patterns but in the clinical environment were reported in Mucor circinelloides , one of the major causative agents of mucormycosis (Lee et al ., , Garcia‐Hermoso et al ., ). To date, similar studies on the global phylogeographic structure of Lichtheimia are non‐existent, although such genetic data are mandatory for preventing the inadvertent intercontinental distribution of highly virulent isolates towards a proper disease management to control outbreaks at a global scale.…”

Advantageous Fungi against Parasites Transmitted through Soil

“…Several reports indicated nosocomial infection by M. circinelloides among immunocompromised people with skin wounds, or suffering diabetes mellitus [51].…”