Bacteriocin-Like Inhibitory Substances from Probiotics as Therapeutic Agents for Candida Vulvovaginitis

Probiotics can potentially prevent and treat diseases. We examined the inhibitory activity of bacteriocin-like inhibitory substances (BLISs) from potentially probiotic lactobacilli and streptococci on Candida albicans and non-Candida albicans clinical isolates from women with vulvovaginitis. Using agar well diffusion assays, BLISs inhibited both Candida albicans and non-Candida albicans isolates. The BLIS from L. pentosus isolates had the highest anti-Candida activity (33/45; 73.3%), followed by BLISs from isolates of L. paracasei subsp. paracasei (31/45; 68.9%), L. rhamnosus I (30/45; 66.7%), L. delbrueckii subsp. lactis I (30/45; 66.7%), and S. uberis II (30/45; 66.7%). Upon characterization according to the retained activity under variable physical and chemical conditions, the BLISs showed stability against heat, pH, and surfactants, but were protease-sensitive, which suggests a proteinaceous nature of the active substances. Using crystal violet assays, the BLISs reduced the Candida biofilm biomass significantly as compared to a control group that lacked BLISs. In vivo testing of the antagonistic activity was performed using the Galleria mellonella (G. mellonella) larvae model. BLISs significantly improved survival in G. mellonella larvae treated with Candida isolates on the first, second, and seventh days, as compared to larvae inoculated with Candida only (p < 0.01). The results show that BLISs can be used as biotherapeutic agents in vulvovaginal candidiasis.

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Optimized 5-Fluorouridine Prodrug for Co-Loading with Doxorubicin in Clinically Relevant Liposomes

Pharmaceutics ◽

10.3390/pharmaceutics13010107 ◽

2021 ◽

Vol 13 (1) ◽

pp. 107

Author(s):

Debra Wu ◽

Douglas Vogus ◽

Vinu Krishnan ◽

Marta Broto ◽

Anusha Pusuluri ◽

...

Keyword(s):

Single Agent ◽

Molar Ratio ◽

Control Group ◽

Drug Tolerability ◽

Breast Cancer Model ◽

In Vivo Testing ◽

Chemical Profiles ◽

Hydrolysis Of ◽

Doxorubicin Liposomes

Liposome-based drug delivery systems have allowed for better drug tolerability and longer circulation times but are often optimized for a single agent due to the inherent difficulty of co-encapsulating two drugs with differing chemical profiles. Here, we design and test a prodrug based on a ribosylated nucleoside form of 5-fluorouracil, 5-fluorouridine (5FUR), with the final purpose of co-encapsulation with doxorubicin (DOX) in liposomes. To improve the loading of 5FUR, we developed two 5FUR prodrugs that involved the conjugation of either one or three moieties of tryptophan (W) known respectively as, 5FUR−W and 5FUR−W3. 5FUR−W demonstrated greater chemical stability than 5FUR−W3 and allowed for improved loading with fewer possible byproducts from tryptophan hydrolysis. Varied drug ratios of 5FUR−W: DOX were encapsulated for in vivo testing in the highly aggressive 4T1 murine breast cancer model. A liposomal molar ratio of 2.5 5FUR−W: DOX achieved a 62.6% reduction in tumor size compared to the untreated control group and a 33% reduction compared to clinical doxorubicin liposomes in a proof-of-concept study to demonstrate the viability of the co-encapsulated liposomes. We believe that the new prodrug 5FUR−W demonstrates a prodrug design with clinical translatability by reducing the number of byproducts produced by the hydrolysis of tryptophan, while also allowing for loading flexibility.

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Candida Albicans ERG11 Gene Polymorphism: Impact on Its In Vivo Virulence and Susceptibility to Fluconazole According to the Galleria Mellonella Model

10.20944/preprints202102.0045.v1 ◽

2021 ◽

Author(s):

Marcel Patindoilba Sawadogo ◽

Adama Zida ◽

Issiaka Soulama ◽

Samuel S Sermé ◽

Thierry Kiswendsida Guiguemdé ◽

...

Keyword(s):

Candida Albicans ◽

Molecular Mechanisms ◽

Reference Strain ◽

Galleria Mellonella ◽

Larval Mortality ◽

Fungal Burden ◽

Significant Difference ◽

Strain Sc5314 ◽

Resistant Strains

The aim of this study is to have an idea on the molecular mechanisms of C. albicans resistance to fluconazole in Burkina Faso, by studying the polymorphism of the ERG11 gene, and its implication in the C. albicans virulence and resistance in vivo according to the Galleria mellonella model; (2) Methods: Ten (10) clinical strains including, 5 resistant and 5 susceptible and 1 virulent and susceptible reference strain SC5314 are used. For the estimation of virulence, the larvae were inoculated with 10 μL of C. albicans cell suspension at variable concentrations: 2,5.105, 5.105, 1.106, and 5.106 CFU/larva of each strain. For the in vivo efficacy study, fluconazole was administered at 1, 4 and 16 mg/kg respectively to G. mellonella larvae, after infection by inoculum 5.106 CFU / larvae of each strain; (3) Results: Six (6) non-silent mutations in the ERG11 gene (K143R, F145L, G307S, S405F, G448E, V456I on ERG11p) were found in 4 resistant isolates. Larval mortality depended on fungal burden and strain. The inoculum 5.106 CFU caused 100% mortality in 2 days for the 2 CAAL-1 and CAAL-2 strains carrying the F145L mutation, in 3 days for the reference strain SC5314, in 4 days for the ensemble of resistant strains, and in 5 days for the ensemble of susceptible strains. The comparison of the mortality due to the reference strain SC5314 CFU / larva and the average mortality due to the two mutant F145L strains, shows a significant difference (P <0.05).Fluconazole significantly protected (P> 0.05) the larvae from infection by susceptible strains and the reference strain. However, 100% mortality in 6 days after injection of the resistant strains, was observed (4) Conclusions: Certain mutations in the ERG11 gene such as the F145L mutation are thought to be a source of increased virulence in Candida albicans. Fluconazole effectively protected larvae from infection by susceptible strains in vivo, unlike resistant strain

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Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01428-13 ◽

2014 ◽

Vol 58 (10) ◽

pp. 5658-5665 ◽

Cited By ~ 11

Author(s):

Yufan Ma ◽

Tingli Lu ◽

Wen Zhao ◽

Ying Wang ◽

Ting Chen ◽

...

Keyword(s):

Lipid Emulsion ◽

Antimalarial Activity ◽

Physical Stability ◽

Aqueous Solubility ◽

Positive Control ◽

Parenteral Administration ◽

Control Group ◽

Content Type ◽

Physical And Chemical

ABSTRACTArtemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, thein vivoantimalarial activities of the lipid emulsions developed were tested inPlasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and thein vivoperformance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation.

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Inhibitory Effect of Lactobacillus plantarum CCFM8724 towards Streptococcus mutans- and Candida albicans-Induced Caries in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4345804 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Qiuxiang Zhang ◽

Sujia Qin ◽

Xianyin Xu ◽

Jianxin Zhao ◽

Hao Zhang ◽

...

Keyword(s):

Candida Albicans ◽

Dental Caries ◽

Oral Cavity ◽

Lactobacillus Plantarum ◽

Streptococcus Mutans ◽

Microbial Colonization ◽

Control Group ◽

Scoring Method ◽

Treatment And Prevention

Streptococcus mutans is a recognized cariogenic bacterium and a major producer of biofilm matrix. The presence of Candida albicans in dental plaque with S. mutans enhances the virulence leading to the onset of rampant caries which is similar to early childhood caries (ECC). The purpose of this study was to explore the effect of Lactobacillus plantarum CCFM8724 (CCFM8724) on the treatment and prevention of dental caries induced by S. mutans and C. albicans in vivo. Rats were divided into 6 groups: the control group and model group, 2 treatment groups, and 2 prevention groups (0.02% chlorhexidine or CCFM8724). The fluctuation of microbial colonization and the change of bacteria flora in rat oral cavity after sowing of L. plantarum CCFM8724 were investigated by colony-forming units (CFU) and microflora analysis. The caries of rats were assessed by microcomputed tomography (micro-CT) and Keyes scoring method. The results showed that L. plantarum CCFM8724 in both the treatment and prevention groups could significantly decrease the population of S. mutans and C. albicans in the rats’ oral cavity ( p < 0.001 ), the mineral loss of enamel ( p < 0.05 ), and the scores of caries ( p < 0.05 ). Besides, L. plantarum CCFM8724 exhibited better effects than chlorhexidine. Hence, L. plantarum CCFM8724 was proved to be a potential oral probiotic on caries treatment and prevention in vivo and it may have the prospect of application in dental caries (especially ECC) prevention products.

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In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

Frontiers in Pharmacology ◽

10.3389/fphar.2021.760768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Arumugam Priya ◽

Anthonymuthu Selvaraj ◽

Dass Divya ◽

Ramalingam Karthik Raja ◽

Shunmugiah Karutha Pandian

Keyword(s):

Early Childhood ◽

Candida Albicans ◽

Streptococcus Mutans ◽

Early Childhood Caries ◽

Galleria Mellonella ◽

Biological Activities ◽

Infective Potential ◽

Childhood Caries

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.

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Effectiveness of a Chlorhexidine Digluconate 0.12% and Cetylpyridinium Chloride 0.05% Solution in eliminating Candida albicans Colonizing Dentures: A Randomized Clinical in vivo Study

The Journal of Contemporary Dental Practice ◽

10.5005/jp-journals-10024-1702 ◽

2015 ◽

Vol 16 (6) ◽

pp. 433-436 ◽

Cited By ~ 5

Author(s):

Antoine Cassia

Keyword(s):

Candida Albicans ◽

Clinical Evidence ◽

Cetylpyridinium Chloride ◽

Test Group ◽

Control Group ◽

Chlorhexidine Digluconate ◽

Denture Stomatitis ◽

Colony Forming Units ◽

Age Range

ABSTRACT Background Effective denture hygiene is important for patients suffering from denture stomatitis (DS). This study aimed to evaluate the efficacy of a solution containing 0.12% chlorhexidine (CHX) digluconate and 0.05% cetylpyridinium chloride (CPC) in eliminating Candida albicans colonizing dentures. Materials and methods Forty denture wearers (11 men, 29 women; age range 40 to 80 years) with clinical evidence of DS were randomly divided into two groups, one test and one control. The dentures of the test group were treated by immersion in a solution of 0.12% CHX and 0.05% CPC while those of the control group were immersed in distilled water. Swabs were collected from the fitting surfaces of the upper dentures prior and post cleaner use and examined mycologically. Results Reduction in the number of colony-forming units (CFU) of Candida albicans after immersion of the dentures in a solution of 0.12% CHX and 0.05% CPC was significantly greater than that of the control group. Conclusion A solution of 0.12% CHX and 0.05% CPC tested as a product of disinfection of the acrylic dentures showed significant results after immersion of 8 night hours for 4 days. How to cite this article Aoun G, Cassia A, Berberi A. Effectiveness of a Chlorhexidine Digluconate 0.12% and Cetylpyridinium Chloride 0.05% Solution in eliminating Candida albicans Colonizing Dentures: A Randomized Clinical in vivo Study. J Contemp Dent Pract 2015;16(6):433-436.

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study the effect of alcoholic and watery extracts of garlic and onion plants on growth of candida albicans and Cryptococcus neoformans in vitro&vivo

The Iraqi Journal of Veterinary Medicine ◽

10.30539/iraqijvm.v32i2.735 ◽

2008 ◽

Vol 32 (2) ◽

pp. 29-38

Author(s):

Abd-Alshaheed D. A.

Keyword(s):

Candida Albicans ◽

Cryptococcus Neoformans ◽

Included Study ◽

Control Group ◽

Alcoholic Extract ◽

Ofcandida Albicans ◽

Group 3 ◽

Group 2

This research included study the effect of garlic and onion plantsextracts(alcoholic and watery) in vitro in three different concentrations15%,25%,35% and in vivo in experimental white mice .Research wasperformed by three experiments, first one was conducted to studyeffectiveness of different concentration of alcoholic and watery garlicextract on growth of candida albicans and Cryptococcus neoformans invitro, showed that the effect of alcoholic extract on the growth of candidaalbicans was inhibitory,started from 0.4 mm to 0.1 mm compared withcontrol plats 4.2 mm ,where as the results of the effect on the growth ofCryptococcus neoformans showed more clearness and the inhibitionstarted from 0.6 to inhibit all the growth in plat in comparison withcontrol plats1.4 mm. While the effect of watery garlic extract showed lesseffect and the inhibition began from 0.5 mm to 0.2 mm for candidaalbicans , but the growth inhibition of Cryptococcus neoformans beganfrom 0.4 to 0.15 mm.The second experiment was the same as the firstexperiment , but using alcoholic and extracts onion , the growth ofcandida albicans inhibited by alcoholic exract from 0.6 mm to no growthin the plat , but the inhibition of Cryptococcus neoformans was startedfrom 0.5mm to 0.2 mm for alcoholic onion extract. While the wateryonion extract effect on the growth of candida albicans the inhibitionstarted from 1.6 mm to 1 mm ,but the inhibition of Cryptococcusneoformans was began from 1 mm to 0.3 mm.Third experiment was study the effect of crude garlic and onion alcoholicextract ointment 1% on experimental infection in mice , using 30experimental mice divided to 6 equal groups,each group include 5 mice*groups which infected with candida albicans treated :The group 1,2,3,expermrutly infected with candida albicans ,where asgroup 3,4,6 were infected with Cryptococcus neoformans for 1,2,3 group,treted with the ointment of alcoholic extract of garlic, group 2 treatedwith alcoholic extract ointment of onion, where as group 3 left with notreatment as a control group

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Search for antifungal compounds using a susceptible strain of Candida albicans and in vivo activity with the Galleria mellonella model

Planta Medica ◽

10.1055/s-0035-1565339 ◽

2015 ◽

Vol 81 (16) ◽

Author(s):

Q Favre-Godal ◽

S Dorsaz ◽

E Ferreira Queiroz ◽

S Ebrahimi ◽

L Marcourt ◽

...

Keyword(s):

Candida Albicans ◽

Galleria Mellonella ◽

Susceptible Strain ◽

Antifungal Compounds

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In vitro and in vivo activity of chelerythrine against Candida albicans and underlying mechanisms

Future Microbiology ◽

10.2217/fmb-2019-0178 ◽

2019 ◽

Vol 14 (18) ◽

pp. 1545-1557 ◽

Cited By ~ 4

Author(s):

Ying Gong ◽

Siwen Li ◽

Weixin Wang ◽

Yiman Li ◽

Wenli Ma ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Calcium Concentration ◽

Galleria Mellonella ◽

Hyphal Growth ◽

Drug Transporter ◽

Antifungal Effect ◽

Underlying Mechanisms

Aim: To evaluate whether chelerythrine (CHT) exhibited antifungal activity against Candida albicans in vitro and in vivo and to explore the underlying mechanisms. Materials & methods: Broth microdilution assay and Galleria mellonella model were used to evaluate the antifungal effect in vitro and in vivo, respectively. Mechanism studies were investigated by morphogenesis observation, Fluo-3/AM, DCFH-DA and rhodamine6G assay, respectively. Results: CHT exhibited antifungal activity against C. albicans and preformed biofilms with minimum inhibitory concentrations ranged from 2 to 16 μg/ml. Besides, CHT protected G. mellonella larvae infected by C. albicans. Mechanisms studies revealed that CHT inhibited hyphal growth, increased intracellular calcium concentration, induced accumulation of reactive oxygen species and inhibited drug transporter activity. Conclusion: CHT exhibited antifungal activity against C. albicans.

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Comparison of antifungal efficacies of moxifloxacin, liposomal amphotericin B, and combination treatment in experimental Candida albicans endophthalmitis in rabbits

Canadian Journal of Microbiology ◽

10.1139/w09-112 ◽

2010 ◽

Vol 56 (1) ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

Yudum Tiftikcioğlu Deren ◽

Şengül Özdek ◽

Ayşe Kalkanci ◽

Nalan Akyürek ◽

Berati Hasanreisoğlu

Keyword(s):

Candida Albicans ◽

Minimum Inhibitory Concentration ◽

Amphotericin B ◽

Combination Treatment ◽

Liposomal Amphotericin ◽

Inhibitory Concentration ◽

Liposomal Amphotericin B ◽

Control Group

The goal of this study was to compare in vitro and in vivo efficacy of moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination treatment against Candida albicans in an exogenous endophthalmitis model in rabbit eyes. Microplate dilution tests and checkerboard analysis were performed to detect in vitro efficacies. Endophthalmitis was induced by intravitreal injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug injection according to prophylactic treatment groups. Group 1 (control group) received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 µg moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 µg liposomal Amp-B/0.1 mL, and group 4 (combi group) both 100 µg moxifloxacin/0.05 mL and 10 µg liposomal Amp-B/0.05 mL intravitreally. Clinical examination, quantitative analysis of microorganisms, and histopathologic examination were performed as in vivo studies. The minimum inhibitory concentration of liposomal Amp-B against C. albicans was found to be 1 µg/mL. Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum inhibitory concentration values of liposomal Amp-B for C. albicans were reduced two- to eightfold with increasing concentrations of moxifloxacin in vitro. In vivo, there was no C. albicans growth in the combi group (zero of eight eyes), whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer loss were found to be lower in the moxi group compared with the control group. Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B against C. albicans in vitro, although it has no in vitro antifungal activity when used alone. It is interesting that we found a synergistic effect for in vitro tests but failed to demonstrate it in vivo. When 100 µg moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are limited to the inner retinal layers.

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