A variety of Candida spp. as the most common fungi in the human body can normally be found in the vagina competing with other microbotes. Their presence is influenced by a variety of conditions in ...the vaginal environment. The proliferation of Candida spp. in the vagina under specific conditions can result in a fungal disease known as vaginal candidiasis. More than 17 species of Candida out of 200 members of this genus are capable of causing diseases within the human body. Estrogen, along with other steroidal hormones, has been shown to have direct multifunctional effects on various pathogenic microorganisms by numerous activities. Its production as well as other factors such as disturbance of microbial balance and immune activity may alter the vaginal physical environment and promote the development of vaginal fungal infection. The vaginal functions can be affected by the level of circulation of estrogens in the blood according to the stage of the menstrual cycle in women. It also has many other functional actions on the vaginal structure. Estrogen and several other factors play an important role in determining the vaginal content of Candida species. Its effect could be a direct action on the cells of Candida or through an indirect effect on the immunity defenses of the vagina.
The photodynamic activities against Candida albicans have been evaluated for seven silicon (IV) phthalocyanines modified axially by different functional groups. The effects of the axial substituents ...on the spectroscopic, photochemical, cellular uptake, and photobiological properties of these silicon phthlaocyanines have been revealed. The dicationic compounds 2 and 4, having two quaternary ammonium groups at the axial positions, exhibit the highest antifungal photocytotoxicity with an IC90 of 61–66 μM, which can be ascribed to their high singlet oxygen quantum yield, non-aggregation nature, effective cellular uptake, and intracellular distribution pattern (localizing preferentially in the mitochondria). By comparison, compounds 2 and 4 show a higher photodynamic inactivation of C. albicans cells than methylene blue (MB), a known antifungal photosensitizer. The IC90 values against C. albicans for 2 and 4 are ca. 8 times lower than that for MB. These results indicate that the dicationic silicon phthalocyanines 2 and 4 are interesting candidates as antifungal photosensitizers for future studies.
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► Photodynamic inactivation of Candida albicans by a series of SiPcs was studied. ► The structure–activity relationship of these silicon phthalocyanines was discussed. ► The dicationic SiPcs 2 and 4 exhibit the highest antifungal photocytotoxicity. ► 2 and 4 show ca. 8 times higher photoactivities than methylene blue.
can form biofilms composed of yeast, hyphal, and pseudohyphal elements, and
cells in the hyphal stage could be a virulence factor. The present study describes the chemical composition, antibiofilm, ...and antihyphal activities of cedar leaf essential oil (CLEO), which was found to possess remarkable antibiofilm activity against
but not to affect its planktonic cell growth. Nineteen components were identified in CLEO by gas chromatography/mass spectrometry, and phenolics were the main constituents. Of these, camphor, fenchone, fenchyl alcohol, α-thujone, and borneol significantly reduced
biofilm formation. Notably, treatments with CLEO, camphor, or fenchyl alcohol at 0.01% clearly inhibited hyphal formation, and this inhibition appeared to be largely responsible for their antibiofilm effects. Transcriptomic analyses indicated that camphor and fenchyl alcohol downregulated some hypha-specific and biofilm related genes (
, and
). Furthermore, camphor and fenchyl alcohol reduced
virulence in a
nematode model. These results demonstrate CLEO, camphor, and fenchyl alcohol might be useful for controlling
infections.
Successful colonization of the acidic vaginal niche by
and
depends on their ability to cope with the presence of lactic and acetic acids produced by commensal microbiota. As such, the inhibitory ...effect of these acids at a low pH in growth of
and
was investigated. The effect of the presence of these organic acids in tolerance of the two
species to azoles used in treatment of vaginal infections was also investigated including eventual synergistic effects. Under the different experimental conditions tested lactic acid exerted no significant inhibitory effect against
or
, contrasting with the generalized impression that the production of this acid is on the basis of the protective effect exerted by vaginal lactobacilii. Differently,
and
exhibited susceptibility to acetic acid, more prominent at lower pHs and stronger for the latter species. Synergism between acetic acid and azoles was observed both for
and
, while lactic acid-azole synergism was only efficient against
. Altogether our
results indicate that tolerance to acetic acid at a low pH may play a more relevant role than tolerance to lactic acid in determining competitiveness in the vaginal tract of
and
including under azole stress. Treatment of vaginal candidiasis with azoles may depend on the level of acetic and lactic acids present and improvements could be achieved synergizing the azole with these acids.
Candida albicans is the most common human yeast pathogen which causes mucosal infections and invasive fungal diseases. Early detection of this pathogen is needed to guide preventative and therapeutic ...treatment. The aim of this study was to establish a polymerase spiral reaction (PSR) assay that rapidly and accurately detects C. albicans and to assess the clinical applicability of PSR-based diagnostic testing. Internal transcribed spacer 2 (ITS2), a region between 5.8S and 28S fungal ribosomal DNA, was used as the target sequence. Four primers were designed for amplification of ITS2 with the PSR method, which was evaluated using real time turbidity monitoring and visual detection using a pH indicator. Fourteen non-C. albicans yeast strains were negative for detection, which indicated the specificity of PSR assay was 100%. A 10-fold serial dilution of C. albicans genomic DNA was subjected to PSR and conventional polimerase chain reaction (PCR) to compare their sensitivities. The detection limit of PSR was 6.9 pg/μl within 1 h, 10-fold higher than that of PCR (69.0 pg/μl). Blood samples (n = 122) were collected from intensive care unit and hematological patients with proven or suspected C. albicans infection at two hospitals in Beijing, China. Both PSR assay and the culture method were used to analyze the samples. Of the 122 clinical samples, 34 were identified as positive by PSR. The result was consistent with those obtained by the culture method. In conclusion, a novel and effective C. albicans detection assay was developed that has a great potential for clinical screening and point-of-care testing.
It is shown that exposure of suspensions of gram-positive Staphylococcus aureus, gram-negative Escherichia coli and yeast-like fungi Candida albicans to laser radiation of blue spectral region with ...405 and 445 nm causes their growth inhibition without prior addition of exogenous photosensitizers. It is experimentally confirmed that compounds of flavin type capable of sensitizing the formation of reactive oxygen species can act as acceptors of optical radiation of blue spectral region determining its antimicrobial effect along with endogenous metal-free porphyrins (the role of endogenous porphyrins has been confirmed earlier by a number of researchers).
The participation of these compounds in the antimicrobial effect of laser radiation is supported by the registration of porphyrin and flavin fluorescence in extracts of microbial cells upon excitation by radiation used to inactivate the pathogens. In addition, the intensity of the porphyrin fluorescence in extracts of microbial cells in the transition from radiation with λ = 405 nm to radiation with λ = 445 nm decreases by 15–30 times, whereas the photosensitivity of the cells under study in this transition decreases only 3.7–6.2 times. The contribution of porphyrin photosensitizers is most pronounced upon exposure to radiation with λ = 405 nm (absorption maximum of the Soret band of porphyrins), and flavins – upon exposure to radiation with λ = 445 nm (maximum in the flavin absorption spectrum and minimum in the absorption spectrum of porphyrins). The ratio between the intensity of the porphyrin and flavin components in the fluorescence spectrum of extracts depends on the type of microbial cells.
•Laser irradiation with λ = 405 nm and 445 nm showed inactivating effect against E. coli, S. aureus, C. albicans in vitro.•Fluorescence studies of microbial cells extracts indicate the presence of endogenous porphyrin and flavin sensitizers.•The contribution of porphyrin sensitizers is maximal upon exposure to radiation with λ = 405 nm and flavins – with 445 nm.•Non-ionic detergent Triton X-100 is proposed to use as extractant of the metal-free porphyrins from microbial cells.•For the first time, the fluorescence of flavin photosensitizers in E. coli extracts was discovered.
Background:
Candida albicans
has emerged as an important nosocomial pathogen. The morbidity and mortality associated with this pathogen are related to the presence of virulence genes and antifungal ...resistance. The objective of the present study was to investigate the prevalence of antifungal resistance, biofilm formation and some virulence genes such as
ALS1
,
PLB1, INT1, SAP1
and
HWP1,
among clinical isolates of
Candida albicans
recovered from immunocompromised patients.
Methods:
The study included one hundred
C. albicans
isolates identified phenotypically and by a molecular technique using Polymerase Chain Reaction (PCR). The identified
C. albicans
was further subjected to antifungal study by the microdilution method, biofilm study and molecular study for virulence genes by PCR.
Results:
The resistance to antifungal drugs, fluconazole, caspofungin and itraconazole was 8% for each of them and for amphotericin B, it was 9%. The prevalence of the studied virulence genes was HWP1 77%, INT1 72%, ALS1 65%, SAP1 65% and PLB1 52%. The biofilm capacity was identified by the microplate method in 58% of
C. albicans
. The OD was intense in 20 isolates, moderate in 21 isolates and mild in 17 isolates. There was a statistically significant increase in the prevalence of the studied virulence genes INT1, ALS1, HWP1, SAP1 and PLB1 among biofilm forming
C. albicans
as compared to non-biofilm forming isolates (
P
=0.0001). Additionally, the resistance to fluconazole, itraconazole and caspofungin was statistically, significantly higher in
C. albicans
with the capacity to form biofilm as compared to non-biofilm forming
C. albicans
.
Conclusion:
The present study highlights the prevalence of resistance to antifungal drugs among
C. albicans
which are not uncommon. Moreover, there was a high prevalence of INT1, ALS1, HWP1, SAP1 and PLB1 genes in
C. albicans
. The resistance to antifungal drugs was common among isolates with the capacity to form the biofilm. There was an association between the biofilm formation and virulence genes.
Due to the increasing prevalence of pathogenic fungal infections, the emergence of antifungal resistant clinical isolates worldwide, and the limited arsenal of available antifungals, developing new ...antifungal strategies is imperative. In this study, we screened a library of 1068 FDA-approved drugs to identify hits that exhibit broad-spectrum antifungal activity. Robenidine, an anticoccidial agent which has been widely used to treat coccidian infections of poultry and rabbits, was identified in this screen. Physiological concentration of robenidine (8 μM) was able to significantly inhibit yeast cell growth, filamentation and biofilm formation of
Candida albicans
– the most extensively studied human fungal pathogen. Moreover, we observed a broad-spectrum antifungal activity of this compound against fluconazole resistant clinical isolates of
C. albicans
,
as well as
a wide range of other clinically relevant fungal pathogens. Intriguingly, robenidine-treated
C. albicans
cells were hypersensitive to diverse cell wall stressors, and analysis of the cell wall structure by transmission electron microscopy (TEM) showed that the cell wall was severely damaged by robenidine, implying that this compound may target the cell wall integrity signaling pathway. Indeed, upon robenidine treatment, we found a dose dependent increase in the phosphorylation of the cell wall integrity marker Mkc1, which was decreased after prolonged exposure. Finally, we provide evidence by RNA-seq and qPCR that Rlm1, the downstream transcription factor of Mkc1, may represent a potential target of robenidine. Therefore, our data suggest that robenidine, a FDA approved anti-coccidiosis drug, displays a promising and broadly effective antifungal strategy, and represents a potentially repositionable candidate for the treatment of fungal infections.
Loss of respiratory functions impairs Candida albicans colonization of host tissues and virulence in a murine model of candidiasis. Furthermore, it is known that respiratory inhibitors decrease ...mannan synthesis and glucan exposure and thereby promotes phagocytosis. To understand the impact of respiratory proteins of C. albicans on host innate immunity, we characterized cell wall defects in three mitochondrial complex I (CI) null mutants (nuo1Δ, nuo2Δ and ndh51Δ) and in one CI regulator mutant (goa1Δ), and we studied the corresponding effects of these mutants on phagocytosis, neutrophil killing and cytokine production by dendritic cells (DCs). We find that reductions of phosphopeptidomannan (PPM) in goa1Δ, nuo1Δ and phospholipomannan (PLM) in nuo2Δ lead to reductions of IL‐2, IL‐4, and IL‐10 but increase of TNF‐α in infected DCs. While PPM loss is a consequence of a reduced phospho‐Cek1/2 MAPK that failed to promote phagocytosis and IL‐22 production in goa1Δ and nuo1Δ, a 30% glucan reduction and a defective Mek1 MAPK response in ndh51Δ lead to only minor changes in phagocytosis and cytokine production. Glucan exposure and PLM abundance seem to remain sufficient to opsonize neutrophil killing perhaps via humoral immunity. The diversity of immune phenotypes in these mutants possessing divergent cell wall defects is further supported by their transcriptional profiles in each infected murine macrophage scenario. Since metabolic processes, oxidative stress‐induced senescence, and apoptosis are differently affected in these scenarios, we speculate that during the early stages of infection, host immune cells coordinate their bioactivities based upon a mixture of signals generated during host‐fungi interactions.
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