MFS multidrug transporters in pathogenic fungi: do they have real clinical impact?

Costa, Catarina; Dias, Paulo Jorge; Sá‐Correia, Isabel; Teixeira, Miguel C.

doi:10.3389/fphys.2014.00197

Cited by 93 publications

(91 citation statements)

References 46 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of these genes can potentially affect infection processes; e.g. the MFS multidrug transporter gene is involved in resistance of fungi to antifungals (Costa et al, 2014), dynamin proteins can play a role in plant resistance to pathogens (Praefcke and McMahon, 2004) and the nor-1 gene is involved in aflatoxin (mycotoxin) biosynthesis in Aspergillus parasiticus (Zhou and Linz, 1999). Furthermore, two annotations show putative involvement in resistance to the antibiotics bleomycin and tetracycline.…”

Section: Yellow Cells Highlight the Annotation For The Avirulence Genmentioning

confidence: 99%

Understanding the structure and variation within the genome of the pathogenic ascomycete fungus Leptosphaeria maculans

Zander¹

View full text Add to dashboard Cite

The ascomycete fungus Leptosphaeria maculans is a major pathogen of Brassica species, particularly canola (Brassica napus; rapeseed; oil-seed rape), and the primary cause of crop losses of canola in Australia, causing blackleg disease. L. maculans, a filamentous ascomycete, is the causal agent of phoma stem canker, commonly referred to as blackleg.In late stages of infection, it spreads through the stem vasculature causing lesions, leading to poor growth, lodging and eventually plant death. This fungus is found in canola-growing regions worldwide such as Australia, Canada and Europe. Increased production of canola in these regions has led to a rise in the severity of the disease. In Australia alone, L. maculans infection is responsible for an estimated Australian $100 million in crop losses each year, with average losses ranging from 15-48 % and significant efforts are underway to improve resistance to this disease.Understanding the characteristics of L. maculans is vital for developing an effective and sustainable approach to the management of blackleg disease on Brassica species. The completion of the L. maculans genome sequence was a significant development in the study of this fungal pathogen and provides a reference genome to which molecular markers can be physically mapped. This has been highly useful in other plant pathogens with sequenced genomes, such as the wheat pathogen Parastagonospora nodorum and the cereal pathogen Fusarium graminearum. Importantly, a reference genome also allows mapping of whole genome re-sequencing data, which is becoming a high-throughput, costeffective method to study genome-wide diversity, particularly for the relatively small, lower complexity genomes of many fungal species. By re-sequencing the genome of different L. maculans isolates, variations in genome sequence and structure can be elucidated.Advances in genome sequencing technologies have revolutionised plant and fungal genomics. They have made genome sequencing, re-sequencing and Single Nucleotide Polymorphism (SNP) discovery highly accessible, high-throughput and cost-effective. The process of whole genome re-sequencing involves aligning millions of short sequence reads to a reference genome sequence. Once this has been achieved, it is possible to identify genetic variation between individuals, which can be linked to variation in phenotype to provide molecular genetic markers and insights into gene function.Sequence variation can have a major impact on how an organism develops and responds to the environment. III | P a g eThis thesis describes the implementation of several approaches to elucidating the genome structure and variation of a number of L. maculans isolates, including SNPs and presence/absence variations (PAVs).Initially, the re-sequencing of two L. maculans isolates for the identification of 21,814 SNPs was performed. I demonstrated the application of a novel SNP calling method, SGSautoSNP and its robustness and sensitivity in identifying polymorphisms in L.maculans. I described the use of these S...

show abstract

Section: Yellow Cells Highlight the Annotation For The Avirulence Genmentioning

confidence: 99%

Understanding the structure and variation within the genome of the pathogenic ascomycete fungus Leptosphaeria maculans

Zander¹

View full text Add to dashboard Cite

show abstract

“…The study in question revealed 20 genes that were significantly upregulated both in vivo and ex vivo in CSF compared to YPD and 6 genes that were significantly upregulated just in in vivo in CSF compared to the other two conditions. Among these, several have the potential to be mediators of FLC or AMB susceptibility, including CFO1 (65,66), ENA1 (67), a 1,4-alpha-glucan-branching enzyme (68), and a gene encoding an unknown MFS transporter, a family of proteins that has been implicated in multidrug resistance via drug efflux (69). While it is likely that some of these genes are also upregulated compared to the expression levels in cells grown under CLSI AFST conditions, it is unclear to what extent the results can be considered generalizable, particularly given the many differences between YPD and RPMI broth, including carbon source (dextrose versus glucose) and pH (6.5 versus 7), the different temperatures at which the isolates were grown (37°C versus 35°C) (5,64,70), and the variability in C. neoformans growth under different conditions (71).…”

Section: Transcriptional Differencesmentioning

confidence: 99%

Physiological Differences in Cryptococcus neoformans Strains In Vitro versus In Vivo and Their Effects on Antifungal Susceptibility

Grossman

Casadevall

2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Cryptococcus neoformans is an environmentally ubiquitous fungal pathogen that primarily causes disease in people with compromised immune systems, particularly those with advanced AIDS. There are estimated to be almost 1 million cases per year of cryptococcal meningitis in patients infected with human immunodeficiency virus, leading to over 600,000 annual deaths, with a particular burden in sub-Saharan Africa. Amphotericin B (AMB) and fluconazole (FLC) are key components of cryptococcal meningitis treatment: AMB is used for induction, and FLC is for consolidation, maintenance and, for occasional individuals, prophylaxis. However, the results of standard antifungal susceptibility testing (AFST) for AMB and FLC do not correlate well with therapeutic outcomes and, consequently, no clinical breakpoints have been established. While a number of explanations for this absence of correlation have been proffered, one potential reason that has not been adequately explored is the possibility that the physiological differences between the in vivo infection environment and the in vitro AFST environment lead to disparate drug susceptibilities. These susceptibility-influencing factors include melanization, which does not occur during AFST, the size of the polysaccharide capsule, which is larger in infecting cells than in those grown under normal laboratory conditions, and the presence of large polyploid "titan cells," which rarely occur under laboratory conditions. Understanding whether and how C. neoformans differentially expresses mechanisms of resistance to AMB and FLC in the AFST environment compared to the in vivo environment could enhance our ability to interpret AFST results and possibly lead to the development of more applicable testing methods.

show abstract

“…Notably, clinical available antifungal agents are limited, and drug resistance is a significant challenge. 2 Yeast-to-hypha transition is a widely acknowledged virulence trait of C. albicans. The transition is controlled by multiple regulatory circuits, among which the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway plays a major role.…”

mentioning

confidence: 99%

Looking intoCandida albicansinfection, host response, and antifungal strategies

Wang

2015

Virulence

View full text Add to dashboard Cite

MFS multidrug transporters in pathogenic fungi: do they have real clinical impact?

Cited by 93 publications

References 46 publications

Understanding the structure and variation within the genome of the pathogenic ascomycete fungus Leptosphaeria maculans

Understanding the structure and variation within the genome of the pathogenic ascomycete fungus Leptosphaeria maculans

Physiological Differences in Cryptococcus neoformans Strains In Vitro versus In Vivo and Their Effects on Antifungal Susceptibility

Looking intoCandida albicansinfection, host response, and antifungal strategies

Contact Info

Product

Resources

About