Analysis of a Food-Borne Fungal Pathogen Outbreak: Virulence and Genome of a
Mucor circinelloides
Isolate from Yogurt
Authors: Lee Soo Chan , Billmyre R. Blake , Li Alicia , Carson Sandra , Sykes Sean M. , Huh Eun Young , Mieczkowski Piotr , Ko Dennis C. , Cuomo Christina A. , Heitman Joseph 
Published: July 2014

Food-borne pathogens are ongoing problems, and new pathogens are emerging. The impact of fungi, however, is largely underestimated. Recently, commercial yogurts contaminated with
Mucor circinelloides
were sold, and >200 consumers became ill with nausea, vomiting, and diarrhea. Mucoralean fungi cause the fatal fungal infection mucormycosis, whose incidence has been continuously increasing. In this study, we isolated an
M. circinelloides
strain from a yogurt container, and multilocus sequence typing identified the strain as
Mucor circinelloides
f.
circinelloides
.
M. circinelloides
f.
circinelloides
is the most virulent
M. circinelloides
subspecies and is commonly associated with human infections, whereas
M. circinelloides
f.
lusitanicus
and
M. circinelloides
f.
griseocyanus
are less common causes of infection. Whole-genome analysis of the yogurt isolate confirmed it as being close to the
M. circinelloides
f.
circinelloides
subgroup, with a higher percentage of divergence with the
M. circinelloides
f.
lusitanicus
subgroup. In mating assays, the yogurt isolate formed sexual zygospores with the (−)
M. circinelloides
f.
circinelloides
tester strain, which is congruent with its
sex
locus encoding SexP, the (+) mating type sex determinant. The yogurt isolate was virulent in murine and wax moth larva host systems. In a murine gastromucormycosis model,
Mucor
was recovered from fecal samples of infected mice for up to 10 days, indicating that
Mucor
can survive transit through the GI tract. In interactions with human immune cells,
M. circinelloides
f.
lusitanicus
induced proinflammatory cytokines but
M. circinelloides
f.
circinelloides
did not, which may explain the different levels of virulence in mammalian hosts. This study demonstrates that
M. circinelloides
can spoil food products and cause gastrointestinal illness in consumers and may pose a particular risk to immunocompromised patients.

IMPORTANCE
The U.S. FDA reported that yogurt products were contaminated with
M. circinelloides
, a mucoralean fungal pathogen, and >200 consumers complained of symptoms, including vomiting, nausea, and diarrhea. The manufacturer voluntarily withdrew the affected yogurt products from the market. Compared to other food-borne pathogens, including bacteria, viruses, and parasites, less focus has been placed on the risk of fungal pathogens. This study evaluates the potential risk from the food-borne fungal pathogen
M. circinelloides
that was isolated from the contaminated commercial yogurt. We successfully cultured an
M. circinelloides
isolate and found that the isolate belongs to the species
M. circinelloides
f.
circinelloides
, which is often associated with human infections. In murine and insect host models, the isolate was virulent. While information disseminated in the popular press would suggest this fungal contaminant poses little or no risk to consumers, our results show instead that it is capable of causing significant infections in animals.