Biology subjects

Elmassry, M. M.

Publications and source records attributed to Elmassry, M. M..

4 recordsLinked to original sources

bioRxiv2024

Global stress response in Pseudomonas aeruginosa upon malonate utilization

Versatility in carbon source utilization assists Pseudomonas aeruginosa in its adaptation to various niches. Recently, we characterized the role of malonate, an understudied carbon source, in quorum sensing regulation, antibiotic resistance, and virulence factor production in P. aeruginosa. These results indicate that global responses to malonate metabolism remain to be uncovered. We leveraged a publicly available metabolomic dataset on human airway and found malonate to be as abundant as glycerol, a common airway metabolite and carbon source for P. aeruginosa. Here, we explored and compared adaptations of P. aeruginosa UCBPP-PA14 (PA14) in response to malonate or glycerol as a sole carbon source using transcriptomics and phenotypic assays. Malonate utilization activated glyoxylate and methylcitrate cycles and induced several stress responses, including oxidative, anaerobic, and metal stress responses associated with increases in intracellular aluminum and strontium. Some induced genes were required for optimal growth of P. aeruginosa in malonate. To assess the conservation of malonate-associated responses among P. aeruginosa strains, we compared our findings in strain PA14 with other lab strains and cystic fibrosis isolates of P. aeruginosa. Most strains grew on malonate as a sole carbon source as efficiently as or better than glycerol. While not all responses to malonate were conserved among strains, formation of biomineralized biofilm-like aggregates, increased tolerance to kanamycin, and increased susceptibility to norfloxacin were the most frequently observed phenotypes. Our findings reveal global remodeling of P. aeruginosa gene expression during its growth on malonate as a sole carbon source that is accompanied by several important phenotypic changes. These findings add to accumulating literature highlighting the role of different carbon sources in the physiology of P. aeruginosa and its niche adaptation. ImportancePseudomonas aeruginosa is a notorious pathogen that causes local and systemic infections in immunocompromised individuals. Different carbon sources can uniquely modulate metabolic and virulence pathways in P. aeruginosa, highlighting the importance of the environment that the pathogen occupies. In this work, we used a combination of transcriptomic analysis and phenotypic assays to determine how malonate utilization impacts P. aeruginosa, as recent evidence indicates this carbon source may be relevant to certain niches associated within the human host. We found that malonate utilization can induce global stress responses, alter metabolic circuits, and influence various phenotypes of P. aeruginosa that could influence host colonization. Investigating the metabolism of malonate provides insight into P. aeruginosa adaptations to specific niches where this substrate is abundant, and how it can be leveraged in the development of much-needed antimicrobial agents or identification of new therapeutic targets of this difficult-to-eradicate pathogen.

microbiology↗

bioRxiv2024

A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules

Changes in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susceptible mice. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of microbiome-host interactions in the context of microbiome-associated diseases.

microbiology↗

bioRxiv2020

Evaluation of the bacterial and fungal microbiome on the skin of Anaxyrus boreas, Rhinella marina, and Xenopus laevis and implications related to Batrachochytrium dendrobatidis susceptibility

The skin and its microbiome are the first lines of defense against environmental stressors and pathogens. The symbiotic relationships between the host and the microbiome and within the microbiome are critical to host health. In frogs, this research area is lacking especially in the context of their skin infection with Batrachochytrium dendrobatidis. B. dendrobatidis is a major fungal skin pathogen to amphibians that has caused the extinction of hundreds of amphibian species populations. While some frog species are known susceptible to B. dendrobatidis infections, and others are resistant, we hypothesized that the skin microbiome of frogs plays a role in the prevention of B. dendrobatidis infections that is yet unknown. Therefore, in this work we have examined the bacterial and fungal skin microbiome of one species that is sensitive to B. dendrobatidis infections, Anaxyrus boreas (formerly: Bufo boreas), and the resistant species, Xenopus laevis and Rhinella marina (formerly: Bufo marinus). This was accomplished using tag-encoded FLX amplicon pyrosequencing (bTEFAP) of the 16S rRNA and ITS DNA regions. Our results showed that the bacterial and fungal skin microbiome of A. boreas and R. marina were more similar than to that of X. laevis. We found distinct patterns between the skin microbiome of B. dendrobatidis sensitive and resistant frog species. For the bacterial microbiome, the most abundant bacterial genus observed in all frog samples was Microbacterium. The resistant species had higher abundance in the genera Pseudomonas, Sphingobium, Pedobacter, Variovorax, Morganella, Sphingomonas, Giesbergeria, and Agromyces. In contrast, they had lower abundance of Elizabethkingia (formerly: Flavobacterium), Enterobacter, Ochrobactrum, Arthobacter, Stenotrophomonas, Shinella, Klebsiella, Aeromonas, Comomonas, Chitinophaga, and Rhodococcus. Regarding the fungal microbiome, the resistant species showed higher abundance in the genera Aspergillus, Cladosporium, Elaphomyces, Monascus, Tritirachium, Ceratostomella, and Claviceps, while Asterotremella, Trichosporon, and Malasezzia genera were less represented in resistant species. We have also observed that in the resistant species, the skin microbiome had higher diversity in the fungal microbiota, but not in the bacterial microbiota. We speculate that those observed differences have implications in B. dendrobatidis susceptibility that are yet to be determined, possibly through competition for nutrients or the production of specific anti-fungal molecules. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2018

GeneHummus: A pipeline to define gene families and their expression in legumes and beyond

During the last decade, plant biotechnological laboratories have sparked a monumental revolution with the rapid development of next sequencing technologies at affordable prices. Soon, these sequencing technologies and assembling of whole genomes will extend beyond the plant computational biologists and become commonplace within the plant biology disciplines. The current availability of large-scale genomic resources for non-traditional plant model systems (the so-called orphan crops) is enabling the construction of high-density integrated physical and genetic linkage maps with potential applications in plant breeding. The newly available fully sequenced plant genomes represent an incredible opportunity for comparative analyses that may reveal new aspects of genome biology and evolution. Analysis of the expansion and evolution of gene families across species is a common approach to infer biological functions. To date, the extent and role of gene families in plants has only been partially addressed and many gene families remain to be investigated. Manual identification of gene families is highly time-consuming and laborious, requiring an iterative process of manual and computational analysis to identify members of a given family, typically combining numerous BLAST searches and manually cleaning data. Due to the increasing abundance of genome sequences and the agronomical interest in plant gene families, the field needs a clear, automated annotation tool. Here, we present the GeneHummus pipeline, a step-by-step R-based pipeline for the identification, characterization and expression analysis of plant gene families. The impact of this pipeline comes from a reduction in hands-on annotation time combined with high specificity and sensitivity in extracting only proteins from the RefSeq database and providing the conserved domain architectures based on SPARCLE. As a case study we focused on the auxin receptor factors gene (ARF) family in Cicer arietinum (chickpea) and other legumes. We anticipate that our pipeline should be suitable for any plant gene family, and likely other gene families, vastly improving the speed and ease of genomic data processing.

bioinformatics↗