Host–pathogen interaction in<i>Candida glabrata</i>infection: current knowledge and implications for antifungal therapy

Rasheed, Mubashshir; Battu, Anamika; Kaur, Rupinder

doi:10.1080/14787210.2020.1792773

Cited by 16 publications

(20 citation statements)

References 130 publications

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“…The model, as such, could be used in the future to test the efficacy of novel antifungal molecules as well as possible novel treatment strategies. Combinatorial antifungal therapies have been proposed, but studies have mainly been carried out in vitro; therefore, their value as antifungal therapy is yet to be established [58]. One other advantage of luminescence imaging is that each animal can be evaluated individually, thereby reducing biological variability, since treatment effectivity can be followed inside the same animal over time.…”

Section: Discussionmentioning

confidence: 99%

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

Schrevens

Sanglard

2021

JoF

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Urinary tract infections (UTIs) are quite common and mainly caused by bacteria such as Escherichia coli. However, when patients have urinary catheters, fungal infections comprise up to 15% of these types of infections. Moreover, fungal UTIs have a high mortality, due to rapid spreading of the fungi to the kidneys. Most fungal UTIs are caused by Candida species, among which Candida albicans and Candida glabrata are the most common. C. glabrata is an opportunistic pathogenic yeast, phylogenetically quite close to Saccharomyces cerevisiae. Even though it is commonly isolated from the urinary tract and rapidly acquires resistance to antifungals, its pathogenesis has not been studied extensively in vivo. In vivo studies require high numbers of animals, which can be overcome by the use of non-invasive imaging tools. One such tool, bioluminescence imaging, has been used successfully to study different types of C. albicans infections. For C. glabrata, only biofilms on subcutaneously implanted catheters have been imaged using this tool. In this work, we investigated the progression of C. glabrata UTIs from the bladder to the kidneys and the spleen. Furthermore, we optimized expression of a red-shifted firefly luciferase in C. glabrata for in vivo use. We propose the first animal model using bioluminescence imaging to visualize C. glabrata in mouse tissues. Additionally, this UTI model can be used to monitor antifungal activity in vivo over time.

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Section: Discussionmentioning

confidence: 99%

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

Schrevens

Sanglard

2021

JoF

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“…As mentioned above, one of the known virulence factors of the C. glabrata complex is its intrinsic low susceptibility to azoles, especially fluconazole [ 7 , 51 , 53 , 67 , 95 , 96 , 97 ]. In general, this is because azoles are the first prophylactic choice against fungal infections due to their low cost, and the second choice for invasive infections produced by different Candida species, generating cross-resistance to the other azoles [ 96 , 98 , 99 , 100 ].…”

Section: Antifungal Resistance Of the C Glabrata Complexmentioning

confidence: 99%

“…As mentioned above, the C. glabrata complex has shown drug resistance to the azoles in several cases, which act by inhibiting the 14-α lanosterol demethylase that is encoded by the ERG11 gene. The ERG11 gene is known to participate in ergosterol biosynthesis [ 97 , 117 ]. Interestingly, Hull et al 2012 found that the isolate of C. glabrata (CG156) has an ERG11 mutation that induces a loss of function associated with cross-resistance to azoles and polyenes.…”

Section: Antifungal Resistance Of the C Glabrata Complexmentioning

confidence: 99%

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

Frías-De-León¹,

Hernández‐Castro

Conde-Cuevas

et al. 2021

Pharmaceutics

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In recent years, a progressive increase in the incidence of invasive fungal infections (IFIs) caused by Candida glabrata has been observed. The objective of this literature review was to study the epidemiology, drug resistance, and virulence factors associated with the C. glabrata complex. For this purpose, a systematic review (January 2001–February 2021) was conducted on the PubMed, Scielo, and Cochrane search engines with the following terms: “C. glabrata complex (C. glabrata sensu stricto, C. nivariensis, C. bracarensis)” associated with “pathogenicity” or “epidemiology” or “antibiotics resistance” or “virulence factors” with language restrictions of English and Spanish. One hundred and ninety-nine articles were found during the search. Various mechanisms of drug resistance to azoles, polyenes, and echinocandins were found for the C. glabrata complex, depending on the geographical region. Among the mechanisms found are the overexpression of drug transporters, gene mutations that alter thermotolerance, the generation of hypervirulence due to increased adhesion factors, and modifications in vital enzymes that produce cell wall proteins that prevent the activity of drugs designed for its inhibition. In addition, it was observed that the C. glabrata complex has virulence factors such as the production of proteases, phospholipases, and hemolysins, and the formation of biofilms that allows the complex to evade the host immune response and generate fungal resistance. Because of this, the C. glabrata complex possesses a perfect pathogenetic combination for the invasion of the immunocompromised host.

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“…Polyenes bind directly to ergosterol in the fungal cell membrane, while azoles target the biosynthesis of this sterol. Echinocandins, on the other hand, target the biosynthesis of glucans in the fungal cell wall [ 19 ]. C. glabrata exhibits intrinsically higher epidemiological cut-off values for azoles compared to other Candida spp and rapidly acquires resistance to azoles [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…C. glabrata exhibits intrinsically higher epidemiological cut-off values for azoles compared to other Candida spp and rapidly acquires resistance to azoles [ 20 ]. Resistance to echinocandins also occurs but is less frequent, while resistance to polyenes is rare [ 19–21 ]. Interestingly, C. glabrata isolates acquiring rapidly resistance often contain mutations in MSH2 , a gene of the DNA mismatch repair pathway [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

et al. 2022

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Candida species are the most commonly isolated opportunistic fungal pathogens in humans. Candida albicans causes most of the diagnosed infections, closely followed by Candida glabrata . C. albicans is well studied, and many genes have been shown to be important for infection and colonization of the host. It is however less clear how C. glabrata infects the host. With the help of fungal RNA enrichment, we here investigated for the first time the transcriptomic profile of C. glabrata during urinary tract infection (UTI) in mice. In the UTI model, bladders and kidneys are major target organs and therefore fungal transcriptomes were addressed in these organs. Our results showed that, next to adhesins and proteases, nitrogen metabolism and regulation play a vital role during C. glabrata UTI. Genes involved in nitrogen metabolism were upregulated and among them we show that DUR1,2 (urea amidolyase) and GAP1 (amino acid permease) were important for virulence. Furthermore, we confirmed the importance of the glyoxylate cycle in the host and identified MLS1 (malate synthase) as an important gene necessary for C. glabrata virulence. In conclusion, our study shows with the support of in vivo transcriptomics how C. glabrata adapts to host conditions.

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Host–pathogen interaction inCandida glabratainfection: current knowledge and implications for antifungal therapy

Cited by 16 publications

References 130 publications

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

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