scholarly journals Evolution of the complex transcription network controlling biofilm formation in Candida species

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eugenio Mancera ◽  
Isabel Nocedal ◽  
Stephen Hammel ◽  
Megha Gulati ◽  
Kaitlin F Mitchell ◽  
...  

We examine how a complex transcription network composed of seven ‘master’ regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. Using a variety of approaches, we observed two major types of changes that have occurred in the biofilm network since the four extant species we examined last shared a common ancestor. Master regulator ‘substitutions’ occurred over relatively long evolutionary times, resulting in different species having overlapping but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.

2020 ◽  
Author(s):  
Eugenio Mancera ◽  
Isabel Nocedal ◽  
Stephen Hammel ◽  
Megha Gulati ◽  
Kaitlin F. Mitchell ◽  
...  

ABSTRACTWe examine how a complex transcription network composed of seven “master” regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. The ability to form biofilms is crucial for microbial colonization of different host niches, particularly when an implanted medical device is present. We examined and compared the network underlying biofilm formation across four Candida species (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis), all of which form biofilms composed of multiple cell types. To describe the salient features of the network across different species, we employed four approaches: (1) we phenotypically characterized the biofilms formed by these species using a variety of methods; (2) we knocked out — one by one — the master regulators identified in C. albicans in the four species and monitored their effect on biofilm formation; (3) we identified the target genes of 18 master regulator orthologs across the four species by performing ChIP-seq experiments; and (4) we carried out transcriptional profiling across each species during biofilm formation. Additional network information was obtained by analyzing an interspecies hybrid formed between the two most closely related species, C. albicans and C. dubliniensis. We observed two major types of changes that have occurred in the biofilm circuit since the four species last shared a common ancestor. Master regulator “substitutions” occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. Both types of change are crucial to account for the structures of the biofilm networks in extant species. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.


2016 ◽  
Vol 6 (01) ◽  
pp. 5218
Author(s):  
Laxmi Mohandas ◽  
Anju T. R. ◽  
Sarita G. Bhat*

An assortment of redox-active phenazine compounds like pyocyanin with their characteristic blue-green colour are synthesized by Pseudomonas aeruginosa, Gram-negative opportunistic pathogens, which are also considered one of the most commercially valuable microorganisms. In this study, pyocyanin from Pseudomonas aeruginosa BTRY1 from food sample was assessed for its antibiofilm activity by micro titer plate assay against strong biofilm producers belonging to the genera Bacillus, Staphylococcus, Brevibacterium and Micrococcus. Pyocyanin inhibited biofilm activity in very minute concentrations. This was also confirmed by Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM). Both SEM and CLSM helped to visualize the biocontrol of biofilm formation by eight pathogens. The imaging and quantification by CLSM also established the impact of pyocyanin on biofilm-biocontrol mainly in the food industry.


2021 ◽  
Vol 22 (7) ◽  
pp. 3666
Author(s):  
Bettina Szerencsés ◽  
Attila Gácser ◽  
Gabriella Endre ◽  
Ildikó Domonkos ◽  
Hilda Tiricz ◽  
...  

The increasing rate of fungal infections causes global problems not only in human healthcare but agriculture as well. To combat fungal pathogens limited numbers of antifungal agents are available therefore alternative drugs are needed. Antimicrobial peptides are potent candidates because of their broad activity spectrum and their diverse mode of actions. The model legume Medicago truncatula produces >700 nodule specific cysteine-rich (NCR) peptides in symbiosis and many of them have in vitro antimicrobial activities without considerable toxicity on human cells. In this work we demonstrate the anticandidal activity of the NCR335 and NCR169 peptide derivatives against five Candida species by using the micro-dilution method, measuring inhibition of biofilm formation with the XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay, and assessing the morphological change of dimorphic Candida species by microscopy. We show that both the N- and C-terminal regions of NCR335 possess anticandidal activity as well as the C-terminal sequence of NCR169. The active peptides inhibit biofilm formation and the yeast-hypha transformation. Combined treatment of C. auris with peptides and fluconazole revealed synergistic interactions and reduced 2-8-fold the minimal inhibitory concentrations. Our results demonstrate that shortening NCR peptides can even enhance and broaden their anticandidal activity and therapeutic potential.


2020 ◽  
Vol 29 (3) ◽  
pp. 37-45
Author(s):  
Mabrouk M Ghonaim ◽  
Azza Z. Labeeb ◽  
Alyaa I. Eliwa ◽  
Eman H. Salem

Background: Accurate and rapid identification of Candida species is necessary for proper diagnosis and treatment of candidiasis due to emergences of drug-resistant strains especially among immunocompromised patients. Objectives: Identification of Candida clinical isolates to the species level using different phenotypic and molecular methods. Biofilm-forming ability and antifungal resistance were also studied. Methodology: Sixty-nine Candida strains were isolated from 220 immunocompromised patients. Identification was performed using chromogenic Candida agar, VITEK 2 system and multiplex polymerase chain reaction (PCR). Biofilm formation was detected by the tube method and antifungal susceptibility was tested using the VITEK2 system. Results: The most common source of Candida isolates was from urine (33.3%) and ICUs (56.6%). VITEK 2 system detected 9 spp.: C. albicans (34.8%), C. tropicalis (21.7%), C. famata (8.7%), C. lusitaniae (7.2%), C. cruzi (7.2%), C. ciferri (5.8%), C. dubliniensis (5.8%), C. parapsilosis (5.8 %) and C. glabrata. Candida isolates showed high resistance to flucytocine (49.3%), and high sensitivity to fluconazole, micafungin, voriconazole and caspofungin (88.4%, 81.2% and 81.2 % respectively). Only 30.4% of all Candida isolates were biofilm producers. There was a positive relationship between antifungal resistance and biofilm formation among Candida isolates. Conclusion: C. albicans was the predominant species. Chromogenic Candida agar and VITEK 2 system were valuable tests compared to PCR in speciation of Candida isolates. Antifungal susceptibility was significantly related to biofilm production and its evaluation is important for proper treatment..


2020 ◽  
Vol 37 (1) ◽  
pp. 83-100
Author(s):  
Abdelhamid , Amira E. ◽  
Zaki , Sanaa M. I. ◽  
Ahmed , Ola I. ◽  
Fathi , Marwa S. M. ◽  
Abu Shady , Nancy M. R.

Microbiology ◽  
2020 ◽  
Vol 166 (9) ◽  
pp. 880-890 ◽  
Author(s):  
Hiroshi Ogasawara ◽  
Toshiyuki Ishizuka ◽  
Shuhei Hotta ◽  
Michiko Aoki ◽  
Tomohiro Shimada ◽  
...  

Under stressful conditions, Escherichia coli forms biofilm for survival by sensing a variety of environmental conditions. CsgD, the master regulator of biofilm formation, controls cell aggregation by directly regulating the synthesis of Curli fimbriae. In agreement of its regulatory role, as many as 14 transcription factors (TFs) have so far been identified to participate in regulation of the csgD promoter, each monitoring a specific environmental condition or factor. In order to identify the whole set of TFs involved in this typical multi-factor promoter, we performed in this study ‘promoter-specific transcription-factor’ (PS-TF) screening in vitro using a set of 198 purified TFs (145 TFs with known functions and 53 hitherto uncharacterized TFs). A total of 48 TFs with strong binding to the csgD promoter probe were identified, including 35 known TFs and 13 uncharacterized TFs, referred to as Y-TFs. As an attempt to search for novel regulators, in this study we first analysed a total of seven Y-TFs, including YbiH, YdcI, YhjC, YiaJ, YiaU, YjgJ and YjiR. After analysis of curli fimbriae formation, LacZ-reporter assay, Northern-blot analysis and biofilm formation assay, we identified at least two novel regulators, repressor YiaJ (renamed PlaR) and activator YhjC (renamed RcdB), of the csgD promoter.


FEBS Letters ◽  
2017 ◽  
Vol 591 (13) ◽  
pp. 2019-2031 ◽  
Author(s):  
Hirotaka Sugino ◽  
Takanori Usui ◽  
Tomohiro Shimada ◽  
Masahiro Nakano ◽  
Hiroshi Ogasawara ◽  
...  

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Tonis Org ◽  
Dan Duan ◽  
Roberto Ferrari ◽  
Amelie Montel-Hagen ◽  
Ben Van Handel ◽  
...  

Understanding the mechanisms directing mesoderm specification holds a great potential to advance the development of cell-based therapies for cardiovascular and blood disorders. The bHLH transcription factor Scl is known as the master regulator of the hematopoietic fate. We recently discovered that, in addition to its critical function in promoting the establishment of hemogenic endothelium during hematopoietic stem/progenitor cell (HS/PC) development, Scl is also required to repress cardiomyogenesis in endothelium in hematopoietic tissues and endocardium in the heart. However, the mechanisms for the cardiac repression have remained unknown. Using ChIP-sequencing and microarray analysis of Flk+ mesoderm differentiated from mouse ES cells, we show that Scl both directly activates a broad gene regulatory network required for hemogenic endothelium and HS/PC development (e.g. Runx1, cMyb, Lyl1, Mef2C, Sox7 etc.), and directly represses transcriptional regulators required for cardiogenesis (e.g. Gata4, Gata6, Myocd, etc.) and mesoderm development (Eomes, Mixl1, Etv2, etc.). Repression of cardiac and mesodermal programs occurs during a short developmental window through Scl binding to distant enhancers, while binding to hematopoietic regulators extends throughout HS/PC and red blood cell development and encompasses both distant and proximal binding sites. We also discovered that, surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic vs. cardiac specification and Scl binding to majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors that facilitate HS/PC emergence from hemogenic endothelium. These results denote Scl as a true master regulator of hematopoietic vs. cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.


2020 ◽  
Vol 21 (17) ◽  
pp. 6131
Author(s):  
Ibeth Guevara-Lora ◽  
Grazyna Bras ◽  
Justyna Karkowska-Kuleta ◽  
Miriam González-González ◽  
Kinga Ceballos ◽  
...  

Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.


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