Emerging infections due to filamentous fungi in humans and animals: only the tip of the iceberg?

Debourgogne, Anne; Dorin, Joséphine; Machouart, Marie

doi:10.1111/1758-2229.12404

Cited by 18 publications

(8 citation statements)

References 60 publications

(93 reference statements)

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“…Over the past decades, there has been a substantial increase in fungal infections worldwide [5,6,7]. It is estimated that over a billion people are affected across the world resulting in approximately 11.5 million life-threatening infections and ~1.5 million deaths annually [4].…”

Section: Introductionmentioning

confidence: 99%

Estimated Burden of Serious Fungal Infections in Ghana

Ocansey¹,

Pesewu

Codjoe

et al. 2019

JoF

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Fungal infections are increasingly becoming common and yet often neglected in developing countries. Information on the burden of these infections is important for improved patient outcomes. The burden of serious fungal infections in Ghana is unknown. We aimed to estimate this burden. Using local, regional, or global data and estimates of population and at-risk groups, deterministic modelling was employed to estimate national incidence or prevalence. Our study revealed that about 4% of Ghanaians suffer from serious fungal infections yearly, with over 35,000 affected by life-threatening invasive fungal infections. Incidence of cryptococcal meningitis, Pneumocystis jirovecii pneumonia, and disseminated histoplasmosis cases in AIDS was estimated at 6275, 12,610 and 724, respectively. Oral and esophageal candidiasis collectively affect 27,100 Ghanaians and 42,653 adult asthmatics are estimated to have fungal asthma. We estimate a prevalence of 12,620 cases of chronic pulmonary aspergillosis (CPA and an incidence of 1254 cases of invasive aspergillosis (IA). Estimated cases of candidemia and candida peritonitis cases were 1446 and 217, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) and tinea capitis was 442,621 and 598,840, respectively. Mucormycosis and fungal keratitis each may affect 58 and 810 Ghanaians. These data highlight the urgent need for intensified awareness to improve diagnosis and management.

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Section: Introductionmentioning

confidence: 99%

Estimated Burden of Serious Fungal Infections in Ghana

Ocansey¹,

Pesewu

Codjoe

et al. 2019

JoF

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“…In comparison with pathogenic bacteria, which have received particular attention for several years, there is a lack of information about the virulence factors and host recognition systems of pathogenic fungi 38 . This hinders the development of new drugs against these microorganisms, while their resistance to current antifungals is progressing quickly 9 , 21 , 39 . Therefore, there is a rush in obtaining information that may contribute to the development of new antifungal agents.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

Martínez-Alarcón

Balloy

Bouchara

et al. 2021

Sci Rep

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Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA from Aspergillus fumigatus known to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.

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“…The development of novel techniques for diagnosis has exposed that, until now, the incidence of fungal infections has been underestimated [1,49]. In comparison with pathogenic bacteria, which have been the focus of attention for several years, there is a lack of information about the virulence factors and host recognition systems of pathogenic fungi [50].…”

Section: Discussionmentioning

confidence: 99%

“…In comparison with pathogenic bacteria, which have been the focus of attention for several years, there is a lack of information about the virulence factors and host recognition systems of pathogenic fungi [50]. This hinders the development of new drugs against these microorganisms, while their resistance to the current ones is progressing quickly [13,24,49]. Therefore, there is an urgent need to obtain information that may contribute to the development of new antifungal agents.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungusScedosporium apiospermum

Martínez-Alarcón

Pieters

Varrot

2020

Preprint

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Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in immunocompromised patients. This fungus exhibits limited susceptibility to all current antifungals and, due its emerging character, its pathogenicity and virulence factors remain largely unknown. Carbohydrate binding proteins such as lectins are involved in host-pathogen interactions and may constitute valuable therapeutic targets to inhibit microbial adhesion to the host cells by using carbohydrate mimics. However, such lectins are still unidentified in S. apiospermum. Here, we present the first report of the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 is homologous to the conidial surface lectin FleA from Aspergillus fumigatus, known to be involved in the adhesion to host glycoconjugates present in human lung epithelium. The present report includes a detailed strategy to achieve SapL1 soluble expression in bacteria, its biochemical characterization, an analysis of its specificity and affinity by glycan arrays and isothermal titration calorimetry (ITC), as well as the structural characterization of its binding mode by X–ray crystallography. The information gathered here contributes to the understanding of glycosylated surface recognition by Scedosporium species and is essential for the design and development of antiadhesive glycodrugs targeting SapL1.Author summaryThe rate of infections caused by the airborne microfungus Scedosporium apiospermum has increased in the recent decades, especially in immunocompromised patients. It represents a therapeutic challenge due to its low susceptibility to all current antifungals, and the subsequent high mortality rate in disseminated scedosporiosis. Recently, the development of antiadhesive therapy has emerged as a novel strategy for the treatment and prevention of fungal infections. It aims to avoid the first step of infections, adhesion, by blocking the proteins responsible for attachment of the pathogens to the host-cells. Unfortunately, in the case of S. apiospermum, those proteins remain unknown but now we have identified a lectin (SapL1) encoded in its genome that is possibly involved in this process. In order to achieve a deep understanding of SapL1 specificity and interactions, we produced recombinant SapL1 in bacteria to carry out its biochemical and structural characterization. As predicted by our bioinformatics studies, SapL1 is a fucose binding lectin and we elucidated the interactions responsible for its binding specificity. Together, these informations should help to design efficient SapL1 inhibitors and therefore to generate potential antiadhesive drugs against this pathogen. Additionally, we have shown that SapL1 belongs to a highly conserved family of lectins that are present in other pathogens. Thus, the information presented here might also be useful for a broad spectrum drug development.

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Emerging infections due to filamentous fungi in humans and animals: only the tip of the iceberg?

Cited by 18 publications

References 60 publications

Estimated Burden of Serious Fungal Infections in Ghana

Estimated Burden of Serious Fungal Infections in Ghana

Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungusScedosporium apiospermum

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