Clonal Dispersal of Cryptococcus gattii VGII in an Endemic Region of Cryptococcosis in Colombia.
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ABSTRACT:
SUBMITTER: Firacative C
PROVIDER: S-EPMC6616963 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Travelling koalas can spread Cryptococcus gattii VGII in Australia
| PRJNA524387 | ENA
Project description:Cryptococcus gattii molecular type VGII is one of the etiologic agents of cryptococcosis, a systemic mycosis affecting a wide range of host species. Koalas (Phascolarctos cinereus) exhibit a comparatively high prevalence of cryptococcosis (clinical and subclinical) and nasal colonization, particularly in captivity. In Australia, disease associated with C. gattii VGII is typically confined to Western Australia and the Northern Territory (with sporadic cases reported in eastern Australia), occupying an enigmatic ecologic niche. A cluster of cryptococcosis in captive koalas in eastern Australia (five confirmed cases, a further two suspected), caused predominantly by C. gattii VGII, was investigated by surveying for subclinical disease, culturing koala nasal swabs and environmental samples, and genotyping cryptococcal isolates. URA5 restriction fragment length polymorphism analysis, multilocus sequence typing (MLST), and whole-genome sequencing (WGS) provided supportive evidence that the transfer of koalas from Western Australia and subsequently between several facilities in Queensland spread VGII into uncontaminated environments and environments in which C. gattii VGI was endemic. MLST identified VGII isolates as predominantly sequence type 7, while WGS further confirmed a limited genomic diversity and revealed a basal relationship with isolates from Western Australia. We hypothesize that this represents a founder effect following the introduction of a koala from Western Australia. Our findings suggest a possible competitive advantage for C. gattii VGII over VGI in the context of this captive koala environment. The ability of koalas to seed C. gattii VGII into new environments has implications for the management of captive populations and movements of koalas between zoos.IMPORTANCECryptococcus gattii molecular type VGII is one of the causes of cryptococcosis, a severe fungal disease that is acquired from the environment and affects many host species (including humans and koalas). In Australia, disease caused by C. gattii VGII is largely confined to western and central northern parts of the country, with sporadic cases reported in eastern Australia. We investigated an unusual case cluster of cryptococcosis, caused predominantly by C. gattii VGII, in a group of captive koalas in eastern Australia. This research identified that the movements of koalas between wildlife parks, including an initial transfer of a koala from Western Australia, introduced and subsequently spread C. gattii VGII in this captive environment. The spread of this pathogen by koalas could also impact other species, and these findings are significant in the implications they have for the management of koala transfers and captive environments.
| S-EPMC6553553 | biostudies-literature
Project description:An outbreak of the fungal pathogen Cryptococcus gattii began in the Pacific Northwest (PNW) in the late 1990s. This outbreak consists of three clonal subpopulations: VGIIa/major, VGIIb/minor, and VGIIc/novel. Both VGIIa and VGIIc are unique to the PNW and exhibit increased virulence. In this study, we sequenced the genomes of isolates from these three groups, as well as global isolates, and analyzed a total of 53 isolates. We found that VGIIa/b/c populations show evidence of clonal expansion in the PNW. Whole-genome sequencing provided evidence that VGIIb originated in Australia, while VGIIa may have originated in South America, and these were likely independently introduced. Additionally, the VGIIa outbreak lineage may have arisen from a less virulent clade that contained a mutation in the MSH2 ortholog, but this appears to have reverted in the VGIIa outbreak strains, suggesting that a transient mutator phenotype may have contributed to adaptation and evolution of virulence in the PNW outbreak. PNW outbreak isolates share genomic islands, both between the clonal lineages and with global isolates, indicative of sexual recombination. This suggests that VGII C. gattii has undergone sexual reproduction, either bisexual or unisexual, in multiple locales contributing to the production of novel, virulent subtypes. We also found that the genomes of two basal VGII isolates from HIV(+) patients contain an introgression tract spanning three genes. Introgression substantially contributed to intra-VGII polymorphism and likely occurred through sexual reproduction with VGI. More broadly, these findings illustrate how both microevolution and sexual reproduction play central roles in the development of infectious outbreaks from avirulent or less virulent progenitors. Importance: Cryptococcus gattii is the causative agent responsible for ongoing infections in the Pacific Northwest of the United States and western Canada. The incidence of these infections increased dramatically in the 1990s and remains elevated. These infections are attributable to three clonal lineages of C. gattii, VGIIa, VGIIb, and VGIIc, with only VGIIa identified once previously in the Pacific Northwest prior to the start of the outbreak, albeit in a less virulent form. This study addresses the origin and emergence of this outbreak, using whole-genome sequencing and comparison of both outbreak and global isolates. We show that VGIIa arose mitotically from a less virulent clonal group, possibly via the action of a mutator phenotype, while VGIIb was likely introduced from Australia, and VGIIc appears to have emerged in the United States or in an undersampled locale via sexual reproduction. This work shows that multiple processes can contribute to the emergence of an outbreak.
| S-EPMC4128362 | biostudies-literature
Project description:Cryptococcus gattii is a pathogenic yeast of humans and other animals which causes disease predominantly in immunocompetent hosts. Infection begins when aerosolized yeast or spores enter the body, triggering an immune response, including engulfment by macrophages. To understand the early transcriptional signals in both the yeast and its mammalian host, we performed a time-course dual-transcriptome sequencing (RNA-seq) experiment for four lineages of C. gattii (lineages VGI to IV) interacting with mouse macrophages at 1, 3, and 6?h postinfection. Comparisons of in vitro to ex vivo gene expression levels indicated that lineage VGII is transcriptionally divergent from non-VGII lineages, including differential expression of genes involved in capsule synthesis, capsule attachment, and ergosterol production. Several paralogous genes demonstrated subfunctionalization between lineages, including upregulation of capsule biosynthesis-related gene CAP2 and downregulation of CAP1 in VGIII. Isolates also compensate for lineage-specific gene losses by overexpression of genetically similar paralogs, including overexpression of capsule gene CAS3 in VGIV, which have lost the CAS31 gene. Differential expression of one in five C. gattii genes was detected following coincubation with mouse macrophages; all isolates showed high induction of oxidative-reduction functions and downregulation of capsule attachment genes. We also found that VGII switches expression of two laccase paralogs (from LAC1 to LAC2) during coincubation of macrophages. Finally, we found that mouse macrophages respond to all four lineages of C. gattii by upregulating FosB/Jun/Egr1 regulatory proteins at early time points. This report highlights the evolutionary breadth of expression profiles among the lineages of C. gattii and the diversity of transcriptional responses at this host-pathogen interface.IMPORTANCE The transcriptional profiles of related pathogens and their responses to host-induced stresses underpin their pathogenicity. Expression differences between related pathogens during host interaction can indicate when and how these genes contribute to virulence, ultimately informing new and improved treatment strategies for those diseases. In this paper, we compare the transcriptional profiles of five isolates representing four lineages of C. gattii in rich media. Our analyses identified key processes, including those involving cell capsule, ergosterol production, and melanin, that are differentially expressed between lineages, and we found that VGII has the most distinct profile in terms of numbers of differentially expressed genes. All lineages have also undergone subfunctionalization for several paralogs, including capsule biosynthesis and attachment genes. Most genes appeared downregulated during coincubation with macrophages, with the largest decrease observed for capsule attachment genes, which appeared to be coordinated with a stress response, as all lineages also upregulated oxidative stress response genes. Furthermore, VGII upregulated many genes that are linked to ergosterol biosynthesis and switched from expression of the laccase LAC1 to expression of LAC2 ex vivo Finally, we saw a pronounced increase in the FosB/Jun/Egr1 regulatory proteins at early time points in bone marrow-derived macrophages, marking a role in the host response to C. gattii This work highlights the dynamic roles of key C. gattii virulence genes in response to macrophages.
| S-EPMC6200987 | biostudies-literature
Project description:Two cats infected by C. gattii, presented lesions on the nasal region and respiratory signs. Strains were typed as molecular type VGII, mating type alpha, MLST subtypes ST442 and ST185. Since Rio de Janeiro is known as an endemic area for C. neoformans VNI, these cases might be a warning for a possible emergence of C. gattii VGII in southeast Brazil.
| S-EPMC6487353 | biostudies-literature
Project description:BackgroundThe absence of Argonaute genes in the fungal pathogen Cryptococcus gattii R265 and other VGII strains indicates that yeasts of this genotype cannot have a functional RNAi pathway, an evolutionarily conserved gene silencing mechanism performed by small RNAs. The success of the R265 strain as a pathogen that caused the Pacific Northwest and Vancouver Island outbreaks may imply that RNAi machinery loss could be beneficial under certain circumstances during evolution. As a result, a hypermutant phenotype would be created with high rates of genome retrotransposition, for instance. This study therefore aimed to evaluate in silicio the effect of retrotransposons and their control mechanisms by small RNAs on genomic stability and synteny loss of C. gattii R265 through retrotransposons sequence comparison and orthology analysis with other 16 C. gattii genomic sequences available.ResultsRetrotransposon mining identified a higher sequence count to VGI genotype compared to VGII, VGIII, and VGIV. However, despite the lower retrotransposon number, VGII exhibited increased synteny loss and genome rearrangement events. RNA-Seq analysis indicated highly expressed retrotransposons as well as sRNA production.ConclusionsGenome rearrangement and synteny loss may suggest a greater retrotransposon mobilization caused by RNAi pathway absence, but the effective presence of sRNAs that matches retrotransposon sequences means that an alternative retrotransposon silencing mechanism could be active in genomic integrity maintenance of C. gattii VGII strains.
| S-EPMC5389150 | biostudies-literature
Project description:Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China.
| S-EPMC8901052 | biostudies-literature
Project description:The genus Cryptococcus comprises more than 80 species, including C. neoformans and C. gattii, which are pathogenic to humans, mainly affecting the central nervous system. The two species differ in geographic distribution and environmental niche. C. neoformans has a worldwide distribution and is often isolated from bird droppings. On the contrary, C. gattii is reported in tropical and subtropical regions and is associated with Eucalyptus species. This review aims to describe the distribution of environmental isolates of the Cryptococcus neoformans species complex and the Cryptococcus gattii species complex in Colombia. A systematic investigation was carried out using different databases, excluding studies of clinical isolates reported in the country. The complex of the species of C. gattii is recovered mainly from trees of the genus Eucalyptus spp., while the complex of the species of C. neoformans is recovered mainly from avian excrement, primarily Columba livia (pigeons) excrement. In addition, greater positivity was found at high levels of relative humidity. Likewise, an association was observed between the presence of the fungus in places with little insolation and cold or temperate temperatures compared to regions with high temperatures.
| S-EPMC8225054 | biostudies-literature
Project description:Cryptococcosis is an infection caused by encapsulated basidiomycetous yeasts belonging to the Cryptococcus neoformans/Cryptococcus gattii species complexes. It is acquired through inhalation of infectious propagules, often resulting in meningitis and meningoencephalitis. The ecological niche of these agents is a wide variety of trees species, as well as pigeon, parrot and passerine excreta. The objective of this study was to isolate Cryptococcus yeasts from excreta of commercially traded parrots and passerines. The 237 samples were collected between October 2018 and April 2019 and processed using conventional methodologies. Nineteen colonies with a dark brown phenotype, caused by phenol oxidase activity, were isolated, suggesting the presence of pathogenic Cryptococcus yeasts. All isolates tested positive for urease activity. URA5-RFLP fingerprinting identified 14 isolates (68.4%) as C. neoformans (genotype AFLP1/VNI) and 5 (26.3%) as C. deuterogattii (genotype AFLP6/VGII). Multi-locus sequence typing was applied to investigate the relatedness of the C. deuterogattii isolates with those collected globally, showing that those originating from bird-excreta were genetically indistinguishable from some clinical isolates collected during the past two decades.
| S-EPMC8807445 | biostudies-literature
Project description:Cryptococcus gattii-induced cryptococcosis is an emerging infectious disease of humans and animals with worldwide distribution and public health importance due to its significant morbidity and mortality rate. The present study aimed to report a case of pulmonary infection by C. gattii molecular type VGII in State of São Paulo, Brazil.A 5-year-old goat showing intermittent dry cough, ruminal tympany, anorexia, fever, tachycardia and tachypnea was presented for necropsy at the Veterinary Hospital of the School of Veterinary Medicine and Animal Sciences, São Paulo University, São Paulo, Brazil. Postmortem examination revealed numerous 2.0-6.0 cm diameter yellow gelatinous pulmonary masses. Tissues were evaluated by a combination of pathological, mycological, and molecular diagnostic techniques. Microscopically, pneumonia granulomatous, multifocal to coalescing, moderate, with many intralesional carminophilic yeasts was observed. The immunohistochemistry and mycological culture confirmed Cryptococcus spp. Internal transcribed spacers and orotidine monophosphate pyrophosphorylase nucleotide differentiation demonstrated that the isolate corresponds to the C. gattii VGII molecular subtype.To our knowledge, this is the first report of a pulmonary infection in a goat linked to C. gattii molecular type VGII in Southeastern Brazil. Our findings emphasize the need for an active surveillance program for human and animal new infections to improve the current public health policies due to expansion of the epidemiological niche of this important microorganism.
| S-EPMC5297049 | biostudies-literature