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Antifungal activity of compounds from Gordonia sp. WA8-44 isolated from the gut of Periplaneta americana and molecular docking studies.

ABSTRACT: Invasive fungal infections are on the rise, leading to a continuous demand for antifungal antibiotics. Rare actinomycetes have been shown to contain a variety of interesting compounds worth exploring. In this study, 15 strains of rare actinobacterium Gordonia were isolated from the gut of Periplaneta americana and screened for their anti-fungal activity against four human pathogenic fungi. Strain WA8-44 was found to exhibit significant anti-fungal activity and was selected for bioactive compound production, separation, purification, and characterization. Three anti-fungal compounds, Collismycin A, Actinomycin D, and Actinomycin X₂, were isolated from the fermentation broth of Gordonia strain WA8-44. Of these, Collismycin A was isolated and purified from the secondary metabolites of Gordonia for the first time, and its anti-filamentous fungi activity was firstly identified in this study. Molecular docking was carried out to determine their hypothetical binding affinities against nine target proteins of Candida albicans. Chitin Synthase 2 was found to be the most preferred antimicrobial protein target for Collismycin A, while 1,3-Beta-Glucanase was the most preferred anti-fungal protein target for Actinomycin D and Actinomycin X₂. ADMET prediction revealed that Collismycin A has favorable oral bioavailability and little toxicity, making it a potential candidate for development as an orally active medication.

SUBMITTER: Liu W

PROVIDER: S-EPMC10395128 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Antifungal activity of compounds from Gordonia sp. WA8-44 isolated from the gut of Periplaneta americana and molecular docking studies.

Liu Wenbin W Li Ertong E Liu Lingyan L Tian Fangyuan F Luo Xiongming X Cai Yanqu Y Wang Jie J Jin Xiaobao X

Heliyon 20230704 7

Invasive fungal infections are on the rise, leading to a continuous demand for antifungal antibiotics. Rare actinomycetes have been shown to contain a variety of interesting compounds worth exploring. In this study, 15 strains of rare actinobacterium Gordonia were isolated from the gut of Periplaneta americana and screened for their anti-fungal activity against four human pathogenic fungi. Strain WA8-44 was found to exhibit significant anti-fungal activity and was selected for bioa ...[more]

PMID: 37539250

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Project description:Background: Germ-free or axenic organisms are valuable tools for studying immunity, digestion, and development in different hosts. Although most of these studies have been conducted on mice, recently, germ-free invertebrate models (e.g. Drosophila and Apis) are used due to their easy husbandry, low cost for production, maintenance and the high number of individuals per generation they produce. However, a limitation of using these insects is the simple bacterial community present in their guts. The gut of the American cockroach Periplaneta americana displays a complex gut bacterial community composed of hundreds of species. Using P. americana, we developed a germ-free omnivorous invertebrate model to investigate how gut bacteria stimulate and shape normal gut development and metabolism. To determine if the insect host is directly affected by the presence of specific members of their bacterial community, gnotobiotic cockroaches were generated by inoculating a set of various P. americana gut-endemic Gram-negative (Bacteroidetes; n=11) and Gram-positive (Firmicutes; n=2) bacterial strains into germ-free insects. Additionally, we were able to recover the ‘normal’ bacterial-induced gut phenotype by co-housing germ-free cockroaches with wildtype P. americana to produce gut-bacteria conventionalized insects. Changes in gene expression profiles from two distinct regions (midgut and hindgut) of P. americana guts were quantified by RNA-Seq analysis of the germfree, gnotobiotic and conventionalized insects. Basic transcriptomics description: High-resolution transcriptome profiling of germ-free, gnotobiotic, and conventionalized treated P. americana midgut and hindguts. Ca. 43 million reads were obtained for each treatment. A de-novo assembly of all sequence reads was performed by Trinity assembler. Transcriptome assembly yielded 369,082 gene models and 554,155 isoforms. After running Trinotate pipeline, 65,047 (12 %) these transcripts matched an annotated product in at least one of the reference databases used (Uniprot, pfam, KEGG, COG). Additionally, 1,008 putative bacterial genes were annotated in the P. americana genome and ultimately excluded from these analyses. After bacteria decontamination, 553,147 assembled isoforms were used for transcript quantification and differential expression analysis using the DESeq2 pipeline. DESeq2 analysis detected 6,730 and 3,958 differentially expressed transcripts among the germ-free, gnotobiotic and conventionalized treatments in P. americana hindgut and midgut, respectively.

Project description:ABSTRACT:Cockroaches are insects that can accommodate diets of different composition, including lignocellulosic materials. Digestion of these compounds is achieved by the insect's own enzymes and also by enzymes produced by gut symbionts. The presence of different and modular bacterial phyla on the cockroach gut tract suggests that this insect could be an interesting model to study the organization of gut bacterial communities associated with the digestion of different lignocellulosic diets. Thus, changes in the diversity of gut associated bacterial communities of insects exposed to such diets could give useful insights on how to improve hemicellulose and cellulose breakdown systems. In this work, through sequence analysis of 16S rRNA clone libraries, we compared the phylogenetic diversity and composition of gut associated bacteria in the cockroach Periplaneta americana collected in the wild-types or kept on two different diets: sugarcane bagasse and crystalline cellulose. These high fiber diets favor the predominance of some bacterial phyla, such as Firmicutes, when compared to wild-types cockroaches. Our data show a high bacterial diversity in P. americana gut, with communities composed mostly by the phyla Bacteroidetes, Firmicutes, Proteobacteria and Synergistetes. Our data show that the composition and diversity of gut bacterial communities could be modulated by diet composition. The increased presence of Firmicutes in sugarcane bagasse and crystalline cellulose-fed animals suggests that these bacteria are strongly involved in lignocellulose digestion in cockroach guts. BACKGROUND:Cockroaches are omnivorous animals that can incorporate in their diets food of different composition, including lignocellulosic materials. Digestion of these compounds is achieved by the insect's own enzymes and also by enzymes produced by gut symbiont. However, the influence of diet with different fiber contents on gut bacterial communities and how this affects the digestion of cockroaches is still unclear. The presence of some bacterial phyla on gut tract suggests that cockroaches could be an interesting model to study the organization of gut bacterial communities during digestion of different lignocellulosic diets. Knowledge about the changes in diversity of gut associated bacterial communities of insects exposed to such diets could give interesting insights on how to improve hemicellulose and cellulose breakdown systems. METHODOLOGY/PRINCIPAL FINDINGS:We compared the phylogenetic diversity and composition of gut associated bacteria in the cockroach P. americana caught on the wild or kept on two different diets: sugarcane bagasse and crystalline cellulose. For this purpose we constructed bacterial 16S rRNA gene libraries which showed that a diet rich in cellulose and sugarcane bagasse favors the predominance of some bacterial phyla, more remarkably Firmicutes, when compared to wild cockroaches. Rarefaction analysis, LIBSHUFF and UniFrac PCA comparisons showed that gene libraries of wild insects were the most diverse, followed by sugarcane bagasse fed and then cellulose fed animals. It is also noteworthy that cellulose and sugarcane bagasse gene libraries resemble each other. CONCLUSION/SIGNIFICANCE:Our data show a high bacterial diversity in P. americana gut, with communities composed mostly by the phyla Bacteroidetes, Firmicutes, Proteobacteria and Synergistetes. The composition and diversity of gut bacterial communities could be modulated by font of diet composition. The increased presence of Firmicutes in sugarcane bagasse and crystalline cellulose-fed animals suggests that these bacteria are strongly involved in lignocellulose digestion in cockroach guts.

Dataset Information

Antifungal activity of compounds from Gordonia sp. WA8-44 isolated from the gut of Periplaneta americana and molecular docking studies.

Publications

Antifungal activity of compounds from <i>Gordonia</i> sp. WA8-44 isolated from the gut of <i>Periplaneta americana</i> and molecular docking studies.

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