Evidence of Microevolution in a Clinical Case of Recurrent Cryptococcus neoformans Meningoencephalitis

Blasi, Elisabetta; Brozzetti, Annalisa; Francisci, Daniela; Neglia, Rachele Giovanna; Cardinali, Gianluigi; Bistoni, Francesco; Vidotto, V.; Baldelli, Franco

doi:10.1007/s100960100549

Cited by 45 publications

(41 citation statements)

References 51 publications

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“…Studies of BF often use Candida strains passaged in laboratories (3,31) that have been adapted to culture media, and thus they may not be representative of BF in clinical strains. Microevolution of fungal pathogens occurs in vitro and in vivo and can affect major virulence factors (5,6,13,14,36). In the present study we determined that BF among clinical Candida strains varied significantly and ranged from high to low.…”

Section: Discussionmentioning

confidence: 67%

Biofilm Formation by and Antifungal Susceptibility of Candida Isolates from Urine

Jain

Kohli

Cook

et al. 2007

Appl Environ Microbiol

123

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Biofilm formation (BF) in the setting of candiduria has not been well studied. We determined BF and MIC to antifungals in Candida spp. isolates grown from urine samples of patients and performed a retrospective chart review to examine the correlation with risk factors. A total of 67 Candida spp. isolates were grown from urine samples from 55 patients. The species distribution was C. albicans (54%), C. glabrata (36%), and C. tropicalis (10%). BF varied greatly among individual Candida isolates but was stable in sequential isolates during chronic infection. BF also depended on the growth medium and especially in C. albicans was significantly enhanced in artificial urine (AU) compared to RPMI medium. In nine of the C. albicans strains BF was 4-to 10-fold higher in AU, whereas in three of the C. albicans strains and two of the C. glabrata strains higher BF was measured in RPMI medium than in AU. Determination of the MICs showed that planktonic cells of all strains were susceptible to amphotericin B (AMB) and caspofungin (CASPO) and that three of the C. glabrata strains and two of the C. albicans strains were resistant to fluconazole (FLU). In contrast, all biofilm-associated adherent cells were resistant to CASPO and FLU. The biofilms of 14 strains (28%) were sensitive to AMB (MIC 50 of <1 g/ml). Correlation between degree of BF and MIC of AMB was not seen in RPMI grown biofilms but was present when grown in AU. A retrospective chart review demonstrated no correlation of known risk factors of candiduria with BF in AU or RPMI. We conclude that BF is a stable characteristic of Candida strains that varies greatly among clinical strains and is dependent on the growth medium. Resistance to AMB is associated with higher BF in AU, which may represent the more physiologic medium to test BF. Future studies should address whether in vitro BF can predict treatment failure in vivo.

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Section: Discussionmentioning

confidence: 67%

Biofilm Formation by and Antifungal Susceptibility of Candida Isolates from Urine

Jain

Kohli

Cook

et al. 2007

Appl Environ Microbiol

123

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“…In this case, IL-10 upregulation resulted in downregulation of excessive inflammation (a drop in the cell count in the CSF), which then permitted proper clearance (14). Several studies have shown that most clinical strains have the ability to vary their phenotypes with respect to colony morphology, polysaccharide structure, and cellular morphology (4,11,21,56), and different colony phenotypes can be observed in primary CSF isolates even before the start of therapy (18). Our data indicate that changes in phenotype translate into different host inflammatory responses and ultimately outcomes.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Switching inCryptococcus neoformansContributes to Virulence by Changing the Immunological Host Response

Guerrero¹,

Fries

2008

Infect Immun

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Cryptococcus neoformans is an encapsulated opportunistic organism that can undergo phenotypic switching. In this process, the parent smooth colony (SM) switches to a more virulent mucoid colony ( ؊/؊ and wild-type mice than in SM-infected mice, whereas tumor necrosis factor alpha levels were higher in SM-infected IL-10 ؊/؊ mice. In conclusion, the MC variant elicits an excessive inflammatory response in a Th1-polarized host environment, and therefore, the outcome is negatively affected by the absence of IL-10.

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“…Therefore, these patients often exhibit for a prolonged time high fungal burdens that promote the selection of switch variants with enhanced virulence which could ultimately result in treatment failure. Several studies have now shown that cryptococcal isolates can exhibit heterogeneous phenotypes with respect to colony morphology, polysaccharide structure, and cellular morphology (2,8,21,50). These studies suggest that most clinical strains have the ability to vary their phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Several observations support the concept that microevolution of C. neoformans occurs during the course of mammalian infection. First, prolonged in vitro and in vivo passage of C. neoformans isolates can result in phenotypic changes associated with differences in virulence, as demonstrated in murine infection models (2,6,8,11,17). Second, serial isolates from chronically infected patients can exhibit differences in virulence (18).…”

mentioning

confidence: 99%

Effects of Antifungal Interventions on the Outcome of Experimental Infections with Phenotypic Switch Variants ofCryptococcus neoformans

Fries¹,

Cook²,

Wang³

et al. 2005

Antimicrob Agents Chemother

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In cryptococcal infection, phenotypic switching from a smooth to a mucoid variant can occur in vivo, producing variants with enhanced virulence that are subsequently selected and affect the outcome of infection. Here, we demonstrate that antifungal treatment of the chronically infected host can promote this phenomenon. Amphotericin B treatment reduces fungal burden less effectively in mucoid variant-infected than in smooth variant-infected mice. Consequently, amphotericin B treatment resulted in a more pronounced prolongation of survival in smooth variant-infected than in mucoid variant-infected mice (20 versus 42 days; P < 0.05). Administration of anticapsular monoclonal antibody mediated better protection in smooth variant-infected than in mucoid variant-infected mice, although a protective effect was not consistently observed at all doses. Most interestingly, both antifungal drug therapy and administration of anticapsular monoclonal antibody promoted the selection of mucoid variants in smooth variant-infected mice, a phenomenon manifested by a statistically higher percentage of mucoid colonies in smooth variant-infected mice than in nontreated control mice. This finding suggests that both chemotherapeutic and immunological antifungal interventions may promote the selection of the more virulent mucoid variant, which could affect the outcome of infection in chronically infected hosts.

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Evidence of Microevolution in a Clinical Case of Recurrent Cryptococcus neoformans Meningoencephalitis

Cited by 45 publications

References 51 publications

Biofilm Formation by and Antifungal Susceptibility of Candida Isolates from Urine

Biofilm Formation by and Antifungal Susceptibility of Candida Isolates from Urine

Phenotypic Switching inCryptococcus neoformansContributes to Virulence by Changing the Immunological Host Response

Effects of Antifungal Interventions on the Outcome of Experimental Infections with Phenotypic Switch Variants ofCryptococcus neoformans

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