The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. Consistent with the morphological transition being regulated by the cAMP-signalling pathway, there is an increase in cellular cAMP levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous cAMP. We have cloned the cyr1 gene encoding adenylate cyclase (AC) and established that its transcript levels correlate with cAMP levels. In addition, we have cloned the genes encoding three Gα (Gpa1–3), Gβ (Gpb1) and Gγ (Gpg1) G proteins. Gpa1 and Gpb1 interact with one another and the N-terminus of AC, but neither Gpa2 nor Gpa3 interacted with Gpb1 or AC. The interaction of Gpa1 with Gpb1 was blocked by GTP, but its interaction with AC was independent of bound nucleotide. The transcript levels for gpa1, gpb1 and gpg1 were similar in mycelium, but there was a transient excess of gpb1 during the transition, and an excess of gpa1 in yeast. We have interpreted our findings in terms of a novel signalling mechanism in which the activity of AC is differentially modulated by Gpa1 and Gpb1 to maintain the signal over the 10 days needed for the morphological switch

Phylogenetic Species of Paracoccidioides spp. Isolated from Clinical and Environmental Samples in a Hyperendemic Area of Paracoccidioidomycosis in Southeastern Brazil

Paracoccidioides brasiliensis complex and P. lutzii are the etiological agents of paracoccidioidomycosis. The geographic distribution of these species in South America is still poorly comprehended. Fifty samples of Paracoccidioides spp. were genotyped, with 46 clinical isolates predominantly isolated in the geographic area of Ribeir&atilde;o Preto, SP, and four environmental isolates collected in Ibi&aacute;, MG, southeastern Brazil. These isolates were evaluated by PCR-RFLP (Restriction Fragment Length Polymorphism) of the tub1 gene and the sequencing of the gp43 exon 2 loci. The species P. lutzii was confirmed by sequencing the internal transcribed spacer (ITS) region of the ribosomal DNA. P. brasiliensis sensu stricto S1b (n = 42) and S1a (n = 5), P. americana (n = 1), P. restrepiensis (n = 1), and P. lutzii (n = 1) were identified among the clinical isolates. All the environmental isolates were characterized as P. brasiliensis sensu stricto S1b. The patient infection by P. lutzii, P. americana (PS2), and one isolate of P. brasiliensis sensu stricto S1b most likely occurred in a geographic area far from the fungal isolation site. No association was found between the infecting genotype and the disease form. These results expand the knowledge of the Paracoccidioides species distribution and emphasize that human migration must also be considered to pinpoint the genotypes in the endemic area

Nanostructured Lipid Carriers Loaded with <i>Lippia sidoides</i> Essential Oil as a Strategy to Combat the Multidrug-Resistant <i>Candida auris</i>

The emerging pathogen Candida auris is an emerging fungal pathogen that was associated with nosocomial infectious outbreaks. Its worldwide incidence and the emerging multidrug-resistant strains highlight the urgency for novel and effective antifungal treatment strategies. Lippia sidoides essential oil (LSEO) proved antifungal activity, including anti-Candida. However, it may undergo irreversible changes when in contact with external agents without adequate protection. Herein, we encapsulated LSEO in nanostructured lipid carriers (NLC) through the hot emulsification method followed by sonication. NLC matrix was based on oleic acid and Compritol® 888, or a combination of carnauba wax and beeswax, stabilized by sodium dodecyl sulfate. Eight formulations were produced and characterized by the determination of the particle size (213.1 to 445.5 nm), polydispersity index (around 0.3), and ζ-potential (−93.1 to −63.8 mV). The antifungal activity of nanoparticles and LSEO against C. auris and the in vivo toxicity in Galleria mellonella model were also evaluated. Both NLC and LSEO exhibited potent activity against the yeast, with Minimum Inhibitory Concentration between 281 and 563 µg/mL, and did not evidence toxicity in the in vivo model. Therefore, this study confirms the viability of NLCs loaded with LSEO in combating drug-resistant pathogens as a potential new therapeutic strategy for managing of candidemia

The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of -1

<p><b>Copyright information:</b></p><p>Taken from "The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of "</p><p></p><p>Molecular Microbiology 2007;65(3):761-779.</p><p>Published online 01 Aug 2007</p><p>PMCID:PMC2064555.</p><p>© 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd</p

The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of -5

<p><b>Copyright information:</b></p><p>Taken from "The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of "</p><p></p><p>Molecular Microbiology 2007;65(3):761-779.</p><p>Published online 01 Aug 2007</p><p>PMCID:PMC2064555.</p><p>© 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd</p