Determination of Epidemiology of Clinically Isolated Cryptococcus neoformans Strains in Japan by Multilocus Sequence Typing

Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha. MLST identified 12 known and five new sequence types (ST). Fourteen STs were identified within the VNI isolates, with ST93 (57/102, 56%) and ST77 (19/102, 19%) being the most prevalent. From the nine VNII isolates previously identify by URA5-RFLP only four (ST40) were confirmed by MLST. The remaining five grouped within the VNB clade in the phylogenetic analysis corresponding to the sequence type ST504. Other two environmental isolates also grouped within VNB clade with the new sequence type ST527. The four VNII/ST40 isolates were isolated from CSF. The two VNIV sequence types (ST11 and ST160) were isolated from blood cultures. Two of six patients evaluated with more than one isolates had mixed infections. Amongst the VNI isolates 4 populations were identified, which showed differences in their susceptibility profiles, clinical outcome and virulence factors. These results reinforce that ST93 is the most prevalent ST in HIV-infected patients in the Southeastern region of Brazil. The finding of the VNB molecular type amongst environmental Brazilian isolates highlights that this genotype is not restricted to the African continent.

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“…neoformans and C . gattii , favoring data comparison and overcoming problems arising from inter-laboratory reproducibility [ 45 – 52 ].…”

Section: Discussionmentioning

confidence: 99%

Genotypic analysis of clinical and environmental Cryptococcus neoformans isolates from Brazil reveals the presence of VNB isolates and a correlation with biological factors

et al. 2018

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“…For example, MLST analyses of several hundred VNI isolates from the United States and a dozen other countries yielded only a few distinct genotypes (designated M1 to M5), of which genotype M5 was the most prevalent (18,20). Subsequent investigations have shown that the M5 is the dominant genotype among clinical isolates from China, Japan, Thailand, and South Korea (34)(35)(36)(37). In contrast to the limited genetic diversity observed among global isolates of VNI, two subpopulations of VNI coexist in southern Africa: (i) strains with SA VNI genotypes that are closely related to the global genotypes of VNI (see Fig.…”

Section: Discussionmentioning

confidence: 99%

Multilocus Sequence Typing of Serially Collected Isolates of Cryptococcus from HIV-Infected Patients in South Africa

Wyk¹,

Govender

Mitchell

et al. 2014

J Clin Microbiol

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cPatients with cryptococcal meningitis in sub-Saharan Africa frequently relapse following treatment. The natural history and etiology of these recurrent episodes warrant investigation. Here, we used multilocus sequence typing (MLST) to compare the molecular genotypes of strains of Cryptococcus neoformans and Cryptococcus gattii isolated from serial episodes of cryptococcal meningitis that were separated by at least 110 days. The most common MLST genotypes among the isolates were the dominant global clinical genotypes (M5 and M4) of molecular type VNI, as well as the VNI genotypes apparently restricted to southern Africa. In addition, there was considerable genetic diversity among these South African isolates, as 15% of the patients had unique genotypes. Eleven percent of the patients were reinfected with a genetically different strain following their initial diagnosis and treatment. However, the majority of serial episodes (89%) were caused by strains with the same genotype as the original strain. These results indicate that serial episodes of cryptococcosis in South Africa are frequently associated with persistence or relapse of the original infection. Using a reference broth microdilution method, we found that the serial isolates of 11% of the patients infected with strains of C. neoformans var. grubii with identical genotypes exhibited >4-fold increases in the MICs to fluconazole. Therefore, these recurrent episodes may have been precipitated by inadequate induction or consolidation of antifungal treatment and occasionally may have been due to increased resistance to fluconazole, which may have developed during the chronic infection.

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“…In addition, data obtained from previous studies of 30 C. neoformans var. grubii isolates (11 VNB, 10 VNI, and 9 VNII) were included in the analysis as outgroup strains (Khayhan et al, 2013; Litvintseva et al, 2006; Sanchini et al, 2014; Cogliati et al, 2013; Meyer et al, 2009; Kaocharoen et al, 2013; Choi et al, 2010; Umeyama et al, 2013; Wiesner et al, 2012) (Table S1). …”

Section: Methodsmentioning

confidence: 99%

Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population

Cogliati

Zani

Rickerts

et al. 2016

Fungal Genetics and Biology

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Cryptococcus neoformans var. neoformans (serotype D) represents about 30% of the clinical isolates in Europe and is present less frequently in the other continents. It is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. Very little is known about the genotypic diversity of this Cryptococcus subtype. The aim of this study was to investigate the genotypic diversity among a set of clinical and environmental C. neoformans var. neoformans isolates and to evaluate the relationship between genotypes, geographical origin and clinical manifestations. A total of 83 globally collected C. neoformans var. neoformans isolates from Italy, Germany, France, Belgium, Denmark, Greece, Turkey, Thailand, Japan, Colombia, and the USA, recovered from different sources (primary and secondary cutaneous cryptococcosis, disseminated cryptococcosis, the environment, and animals), were included in the study. All isolates were confirmed to belong to genotype VNIV by molecular typing and they were further investigated by MLST analysis. Maximum likelihood phylogenetic as well as network analysis strongly suggested the existence of a recombinant rather than a clonal population structure. Geographical origin and source of isolation were not correlated with a specific MLST genotype. The comparison with a set of outgroup C. neoformans var. grubii isolates provided clear evidence that the two varieties have different population structures.

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Determination of Epidemiology of Clinically Isolated Cryptococcus neoformans Strains in Japan by Multilocus Sequence Typing

Cited by 23 publications

References 15 publications

Genotypic analysis of clinical and environmental Cryptococcus neoformans isolates from Brazil reveals the presence of VNB isolates and a correlation with biological factors

Genotypic analysis of clinical and environmental Cryptococcus neoformans isolates from Brazil reveals the presence of VNB isolates and a correlation with biological factors

Multilocus Sequence Typing of Serially Collected Isolates of Cryptococcus from HIV-Infected Patients in South Africa

Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population

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