乳杆菌抑制黄曲霉孢子萌发的研究

为探讨乳杆菌抑制黄曲霉孢子萌发的可能机制 ,在乳杆菌培养液、乳杆菌培养液的上清液和乳杆菌的细胞悬浮液中接种一定量的黄曲霉孢子 ,每隔 4h分别取少量液体在PDA平板上进行霉菌计数 ,直到 30h。 2 8℃培养 72h后计数萌发的霉菌孢子。结果表明 :只有乳杆菌培养液组对黄曲霉孢子萌发有显著的抑制作用 ,说明乳杆菌抑制黄曲霉孢子萌发的可能机制是低pH值 ,乳杆菌的代谢产物与微生物间竞争多因素协同作用的结果。     

Melanin as a virulence factor in pathogenic fungi

The pigment melanin is found universally in nature and is attributed to a variety of functions. In some fungi it is thought to play a decisive role in the determination of virulence. This review examines the experimental evidence which has led to an understanding of the mechanisms by which melanin functions in pathogenic fungi, particularly in plant pathogens, in Cryptococcus neoformans and Wangiella dermatitidis.     

EFFICACY OF MICONAZOLE IN EXPERIMENTAL KERATOMYCOSIS

For the first time comparative efficacy of 1 % miconazole in ointment base and drops has been evaluated against Candida, Aspergillus and Fusarium organisms In experimental heratomycosis. The findings of the present study reveal that miconazole in ointment drug delivery system has the advantage of being more effective in healing the fungal ulcers and associated lesions. It requires much less frequent application than drops, a parameter of great importance in improving patient compliance. Miconazole ointment was well tolerated by the rabbit eye and produced no ocular or systemic toxicity. The present study confirms that miconazole is a broad-spectrum antifungal agent and it could be a better alternative to presently available drugs to treat human heratomycosis .     

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure

Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.     

Cloning and expression of the cDNA encoding an alternative oxidase gene from Aspergillus niger WU-2223L

A cDNA fragment encoding the mitochondrial alternative oxidase, the enzyme responsible for cyanide-insensitive and salicylhydroxamic acid (SHAM)-sensitive respiration, from the citric acid-producing fungus Aspergillus niger WU-2223L was cloned and expressed in Escherichia coli as a host strain. Synthetic primers were designed from the conserved nucleotide sequences of the alternative oxidase genes from higher plants and a yeast. The 210-bp DNA fragment was amplified by PCR with these primers using chromosomal DNA of WU-2223L as a template, and was employed to screen a cDNA library of A. niger. One full-length cDNA clone of 1.2 kb was obtained, and was sequenced to reveal that the clone contained an open reading frame (ORF-AOX1) encoding a polypeptide of 351 amino acids. The predicted amino-acid sequence exhibited 50%, 55%, and 52% homology to the alternative oxidases of Hansenula anomala, Neurospora crassa and Sauromatum guttatum, respectively. In the 5′-terminus region of the ORF-AOX1, a mitochondrial targeting motif was found. The whole open reading frame of ORF-AOX1 was ligated to plasmid pKK223-3 to construct the expression vector pKAOX1. The E. coli transformant harboring pKAOX1 showed cyanide-insensitive and SHAM-sensitive respiration, and expression was increased approximately two-fold by the addition of IPTG. These results indicated that the ORF-AOX1 encodes an alternative oxidase of A. niger. Received: 10 August / 13 October 1998     

Microscopic studies on the Aspergillus flavus infected kernels of commercial peanuts in Georgia

This article describes the use of microscopy to prove the presence of the aflatoxin producing pathogen, Aspergillus flavus Link ex Fries in commercially available edible peanuts in Georgia. Light microscopy in combination with electron microscopy has been used to describe the infection course established by the fungus. The alkali maceration technique used in the study was successful and sufficient to detect the kernel infection of A. flavus and monitor the infection percentage in edible peanuts. Percentage of infected kernel varied from one commercial outlet to another in the region. Briefly, peanut seeds from Cartersville had the highest percentage of A. flavus infection. Electron microscopy confirmed the seed-borne infection of this mold. Mycelium established inside the host tissues both intercellularly and intracellularly aided by active, continuous branching of young hyphae. Establishment of mycelium was also detected in the xylem vessels of roots indicative of systemic infection. Thus, edible peanuts can form an important source of inoculum and facilitate the spread of the fungus from one peanut to another in commercial outlets and elsewhere. Present study provides strong evidence that A. flavus can escape detection at selling points and lands in commercial outlets via edible peanuts. That these contaminated peanuts could pose public health hazards is discussed.     

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections

Introduction: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality.

Areas covered: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or C_min/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2–4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI.

Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.     

紫外线对真菌的杀灭作用

实验室试验证明,以强度为350μW/cm~2杀菌紫外线照射平皿中真菌悬液时,酵母菌抗力最低,青霉与镰刀菌其次,黄曲霉及交链孢霉最强.紫外线可使黄曲霉产毒能力增加。     

Effect of Jianpi-yangwei decoction on gut fungi in the patients with gastric cancer undergoing chemotherapy

Background:Our previous study shows that the empirical formula of Chinese medicine Jianpi-yangwei decoction(JYD)can improve the quality of life in patients with gastric cancer undergoing chemotherapy by increasing beneficial gut bacteria and decreasing harmful bacteria.The present study aims to investigate the effect of JYD on gut fungi in patients with gastric cancer undergoing chemotherapy.Methods:A total of 73 patients with gastric cancer undergoing chemotherapy were recruited.Twenty-nine patients in the chemotherapy group were given standard chemotherapy and 44 patients in the observation group were given JYD plus standard chemotherapy.A control group(55 cases)was recruited from the healthy medical examiners.After 3 months of treatment,life-quality score was evaluated and fecal microbiota was tested by high-throughput sequencing based on the 18S rRNA gene.Results:After treatment,life-quality score in the observation group was significantly lower than that in the chemotherapy group(P<0.05).There was no significant difference between the observation and control groups’diversity and richness indices of intestinal fungi.The Chao index for intestinal fungi in the chemotherapy group was significantly lower than that in the observation group(P<0.05).There was a significant difference between the control and chemotherapy groups in the intestinal fungi according to Shannon and Simpson indices(P<0.05).Linear discriminant analysis effect size analysis showed no significant differences among the three groups,but significant difference in intestinal fungi was observed between the observation group and the chemotherapy group.At the genus level,the relative abundance of the Aspergillus genus in the observation and control groups was significantly lower(P<0.05),the relative abundance of the Cutaneotrichosporon,Galactomyces,and Ganoderma genus taxa was significantly higher compared with those in the chemotherapy group(P<0.05),and there was no significant difference between the observation group and control group.Conclusion:JYD can ameliorate chemotherapy-induced fungal dysbacteriosis in patients with gastric cancer undergoing chemotherapy and improve the quality of life of patients.