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Clinical Microbiology and Infection :... Jul 2019Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause... (Review)
Review
BACKGROUND
Recently there has been an increase in Candida infections worldwide. A handful of species in the genus Candida are opportunistic pathogens and have been known to cause infections in immunocompromised or otherwise impaired hosts. These infections can be superficial, affecting the skin or mucous membrane, or invasive, which can be life-threatening. Azoles and echinocandins are antifungal drugs used globally to treat Candida infections. However, resistance to these antifungal drugs has increased in many of the Candida species, and the effects this has in the clinical setting can be seen.
OBJECTIVES
Here, we discuss the mechanisms that Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris are implementing to increase resistance to azoles and echinocandins, and how they are affecting clinical, or hospital, settings worldwide.
SOURCES
Different studies and papers describing the mechanisms of antifungal drugs and Candida species evolution to becoming resistant to these drugs were looked at for this review.
CONTENT
We discuss the mechanisms that azoles and echinocandins use against Candida species to treat infections, as well as the evolution of these fungi to become resistant to these drugs, and the effect this has in the clinical settings around the globe.
IMPLICATIONS
Increased resistance to azoles and echinocandins by Candida species is an increasingly serious problem in clinical settings worldwide. Understanding the mechanisms used against antifungal drugs is imperative for patient treatment.
Topics: Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Drug Resistance, Multiple, Fungal; Echinocandins; Humans; Microbial Sensitivity Tests
PubMed: 30965100
DOI: 10.1016/j.cmi.2019.03.028 -
Expert Review of Respiratory Medicine Jul 2020Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised... (Review)
Review
INTRODUCTION
Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised individuals. The diagnostic approach for many fungal pathogens continues to evolve. Herein, we outline available diagnostic tests for the most common fungal infections with a focus on recent advances and future directions.
AREAS COVERED
We discuss the diagnostic testing methods for angioinvasive molds ( spp. and spp.), invasive yeast ( spp. and ssp.), Pneumocystis, and endemic fungi ( sp., Coccidioides sp., and Hitoplasma sp.). The PubMed-NCBI database was searched within the past 5 years to identify the most recent available literature with dates extended in cases where literature was sparse. Diagnostic guidelines were utilized when available with references reviewed.
EXPERT OPINION
Historically, culture and/or direct visualization of fungal organisms were required for diagnosis of infection. Significant limitations included ability to collect specimens and delayed diagnosis associated with waiting for culture results. Antigen and antibody testing have made great strides in allowing quicker diagnosis of fungal infections but can be limited by low sensitivity/specificity, cross-reactivity with other fungi, and test availability. Molecular methods have a rich history in some fungal diseases, while others continue to be developed.
Topics: Aspergillus; Blastomyces; Candida; Coccidioides; Cryptococcus; Histoplasma; Humans; Lung Diseases, Fungal; Mucor; Pneumocystis; Pneumonia
PubMed: 32290725
DOI: 10.1080/17476348.2020.1753506 -
Infection, Genetics and Evolution :... Apr 2021Cryptococcus neoformans is a dimorphic fungus that causes lethal meningoencephalitis mainly in immunocompromised individuals. Different morphotypes enable this... (Review)
Review
Cryptococcus neoformans is a dimorphic fungus that causes lethal meningoencephalitis mainly in immunocompromised individuals. Different morphotypes enable this environmental fungus and opportunistic pathogen to adapt to different natural niches and exhibit different levels of pathogenicity in various hosts. It is well-recognized that C. neoformans undergoes bisexual or unisexual reproduction in vitro to generate genotypic, morphotypic, and phenotypic diversity, which augments its ability for adaptation. However, if and how sexual reproduction and the meiotic machinery exert any direct impact on the infection process is unclear. This review summarizes recent discoveries on the regulation of cryptococcal life cycle and morphogenesis, and how they impact cryptococcal pathogenicity. The potential role of the meiotic machinery on ploidy regulation during cryptococcal infection is also discussed. This review aims to stimulate further investigation on links between fungal morphogenesis, sexual reproduction, and virulence.
Topics: Cryptococcus neoformans; Humans; Morphogenesis; Reproduction; Virulence
PubMed: 33497839
DOI: 10.1016/j.meegid.2021.104731 -
Microbiology (Reading, England) Sep 2020is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans... (Review)
Review
is a lethal fungus disguised in a polysaccharide coat. It can remain dormant in the host for decades prior to reactivation, causing systemic cryptococcosis in humans and other mammals. deploys a multitude of traits to adapt to and survive within the host, including immunosuppression, an ability to replicate intra- and extra-cellularly in phagocytes, changes in morphology and ploidy, a predilection to infect the CNS, and the capacity to utilize neurotransmitters and unique carbon sources available in the brain. These pathogenic strategies displayed by this fungus might have evolved through its interactions with microbial predators in the environment.
Topics: Adaptation, Physiological; Animals; Cryptococcosis; Cryptococcus neoformans; Genome, Fungal; Humans; Phylogeny; Virulence
PubMed: 32956032
DOI: 10.1099/mic.0.000973 -
Virulence Dec 2022Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and... (Review)
Review
Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and antifungal susceptibility pattern is necessary to control and treat candidiasis. We aimed to systematically analyse the susceptibility profiles of species published in the last ten years (December 2011 to December 2021) from mainland China. The studies were collected from PubMed, Google Scholar, and Science Direct search engines. Out of 89 included studies, a total of 44,716 isolates were collected, mainly comprising (49.36%), (21.89%), (13.92%), and (11.37%). The lowest susceptibility was detected for azole group; fluconazole susceptibilities against , and were 93.25%, 91.6%, 79.4%, 77.95%, 76%, 50%, and 0% respectively. Amphotericin B and anidulafungin were the most susceptible drugs for all species. Resistance to azole was mainly linked with mutations in , and genes. Mutation in and in and causing resistance to echinocandins was stated in two studies. Gaps in the studies' characteristics were detected, such as 79.77%, 47.19 %, 26.97%, 7.86%, and 4.49% studies did not mention the mortality rates, age, gender, breakpoint reference guidelines, and fungal identification method, respectively. The current study demonstrates the overall antifungal susceptibility pattern of species, gaps in surveillance studies and risk-reduction strategies that could be supportive in candidiasis therapy and for the researchers in their future studies.
Topics: Humans; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 36120738
DOI: 10.1080/21505594.2022.2123325 -
Plant Biotechnology Journal Sep 2021Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the...
Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development of Spray-Induced Gene Silencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Aspergillus niger and Verticillium dahliae, but no uptake in Colletotrichum gloeosporioides, and weak uptake in a beneficial fungus, Trichoderma virens. For the oomycete plant pathogen, Phytophthora infestans, RNA uptake was limited and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen's RNA uptake efficiency.
Topics: Ascomycota; Botrytis; Colletotrichum; Gene Silencing; Plant Diseases; RNA Interference; RNA, Double-Stranded; Rhizoctonia
PubMed: 33774895
DOI: 10.1111/pbi.13589 -
Medical Mycology Journal 2022This review describes the changes in yeast species names in the previous decade. Several yeast species have been reclassified to accommodate the "One fungus=One name"... (Review)
Review
This review describes the changes in yeast species names in the previous decade. Several yeast species have been reclassified to accommodate the "One fungus=One name" (1F=1N) principle of the Code. As the names of medically important yeasts have also been reviewed and revised, details of the genera Candida, Cryptococcus, Malassezia, and Trichosporon are described in Section 3, along with the history of name changes. Since the phylogenetic positions of Candida species in several clades have not been clarified, revision of this species has not been completed. Among the species that remain unrevised despite their importance in the medical field, we propose the transfer of six Candida species to be reclassified in the Nakaseomyces clade, including Nakaseomyces glabratus and Nakaseomyces nivalensis.
Topics: Trichosporon; Malassezia; Cryptococcus; Candida; Phylogeny
PubMed: 36450564
DOI: 10.3314/mmj.22.004 -
Frontiers in Cellular and Infection... 2021While most fungi have the ability to reproduce sexually, multiple independent lineages have lost meiosis and developed parasexual cycles in its place. Emergence of... (Review)
Review
While most fungi have the ability to reproduce sexually, multiple independent lineages have lost meiosis and developed parasexual cycles in its place. Emergence of parasexual cycles is particularly prominent in medically relevant fungi from the CUG paraphyletic group of species. Since the discovery of parasex in roughly two decades ago, it has served as the model for species. Importantly, parasex in retains hallmarks of meiosis including genetic recombination and chromosome segregation, making it a potential driver of genetic diversity. Furthermore, key meiotic genes play similar roles in parasex and highlights parallels between these processes. Yet, the evolutionary role of parasex in adaptation and the extent of resulting genotypic and phenotypic diversity remain as key knowledge gaps in this facultative reproductive program. Here, we present our current understanding of parasex, the mechanisms governing its regulation, and its relevance to biology.
Topics: Biological Evolution; Candida; Candida albicans; Genotype; Meiosis
PubMed: 34966696
DOI: 10.3389/fcimb.2021.796929 -
PLoS Pathogens Aug 2023Fungal infections are rising, with over 1.5 billion cases and more than 1 million deaths recorded each year. Among these, Candida infections are frequent in at-risk...
Fungal infections are rising, with over 1.5 billion cases and more than 1 million deaths recorded each year. Among these, Candida infections are frequent in at-risk populations and the rapid development of drug resistance and tolerance contributes to their clinical persistence. Few antifungal drugs are available, and their efficacy is declining due to the environmental overuse and the expansion of multidrug-resistant species. One way to prolong their utility is by applying them in combination therapy. Here, we highlight recently described azole potentiators belonging to different categories: natural, repurposed, or novel compounds. We showcase examples of molecules and discuss their identified or proposed mode of action. We also emphasise the challenges in azole potentiator development, compounded by the lack of animal testing, the overreliance on Candida albicans and Candida auris, as well as the limited understanding of compound efficacy.
Topics: Animals; Candida; Candida albicans; Candidiasis; Antifungal Agents; Azoles
PubMed: 37651385
DOI: 10.1371/journal.ppat.1011583 -
PeerJ 2022Moonlighting proteins represent an intriguing area of cell biology, due to their ability to perform two or more unrelated functions in one or many cellular compartments.... (Review)
Review
Moonlighting proteins represent an intriguing area of cell biology, due to their ability to perform two or more unrelated functions in one or many cellular compartments. These proteins have been described in all kingdoms of life and are usually constitutively expressed and conserved proteins with housekeeping functions. Although widely studied in pathogenic bacteria, the information about these proteins in pathogenic fungi is scarce, but there are some reports of their functions in the etiological agents of the main human mycoses, such as spp., , , , , and . In these fungi, most of the described moonlighting proteins are metabolic enzymes, such as enolase and glyceraldehyde-3-phosphate dehydrogenase; chaperones, transcription factors, and redox response proteins, such as peroxiredoxin and catalase, which moonlight at the cell surface and perform virulence-related processes, contributing to immune evasion, adhesions, invasion, and dissemination to host cells and tissues. All moonlighting proteins and their functions described in this review highlight the limited information about this biological aspect in pathogenic fungi, representing this a relevant opportunity area that will contribute to expanding our current knowledge of these organisms' pathogenesis.
Topics: Humans; Mycoses; Virulence; Paracoccidioides; Cryptococcus neoformans; Histoplasma
PubMed: 36117533
DOI: 10.7717/peerj.14001