Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of Mucor circinelloides f. circinelloides resolved by whole genome sequencing

Garcia-Hermoso, D.; Criscuolo, A.; Lee, S. c.; Legrand, M.; Chaouat, M.; Denis, B.; Lafaurie, M.; Rouveau, M.; Soler, C.; Schaal, J.-V.; Mimoun, M.; Mebazaa, A.; Heitman, J.; Francoise, D.; Brisse, S.; Stephane, B.; Alanio, A.

doi:10.1101/233049

bioRxiv · 10.1101/233049

Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of Mucor circinelloides f. circinelloides resolved by whole genome sequencing

Garcia-Hermoso, D.·Criscuolo, A.·Lee, S. c.·Legrand, M.·Chaouat, M.·Denis, B.·Lafaurie, M.·Rouveau, M.·Soler, C.·Schaal, J.-V.·Mimoun, M.·Mebazaa, A.·Heitman, J.·Francoise, D.·Brisse, S.·Stephane, B.·Alanio, A.

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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.\n\nWe analyzed M. circinelloides isolates from patients in our burn unit (BU1) together with non-outbreak isolates from burn unit 2 (BU2, Paris area) and from France over a two-year period (2013-2015). For each isolate, WGS and a de novo genome assembly was performed from read data extracted from the aligned contig sequences of the reference genome (1006PhL).\n\nA total of 21 isolates were sequenced including 14 isolates from six BU1 patients. Phylogenetic classification showed that the clinical isolates clustered in four highly divergent clades. Clade1 contained at least one of the strains from the six epidemiologically-linked BU1 patients. The clinical isolates seemed 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 shared one strain in BU1, suggesting direct transmission or contamination with the same environmental source.\n\nWGS coupled with precise epidemiological data and analysis of several isolates per patients revealed in our study a complex situation with both potential cross-transmission and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.\n\nImportanceInvasive wound mucormycosis (IWM) is a severe infection due to the environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used Whole Genome Sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient-specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission between the patients. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on whole genome sequencing and careful sampling.

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Garcia-Hermoso, D., Criscuolo, A., Lee, S. c., Legrand, M., Chaouat, M., Denis, B., Lafaurie, M., Rouveau, M., Soler, C., Schaal, J.-V., Mimoun, M., Mebazaa, A., Heitman, J., Francoise, D., Brisse, S., Stephane, B., Alanio, A.. 2017-12-12. Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of Mucor circinelloides f. circinelloides resolved by whole genome sequencing. https://doi.org/10.1101/233049

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