Browsing by Author "Piedl, Karla"
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- Bokeelamides: Lipopeptides from Bacteria Associated with Marine Egg MassesCampbell, Rose; Kyei, Lois; Piedl, Karla; Zhang, Zheye; Chen, Ming; Mevers, Emily (American Chemical Society, 2024-11)Moon snails (family: Naticidae) lay egg masses that are rich in bacterial species distinct from the surrounding environment. We hypothesized that this microbiome chemically defends the moon snail eggs from predation and pathogens. Herein, we report the discovery of bokeelamides, new lipopeptides from the egg mass-associated bacterium, Ectopseudomonas khazarica, which were discovered using mass spectrometry (MS)-based metabolomics. The structures of the bokeelamides were elucidated using two-dimensional (2D) nuclear magnetic resonance (NMR), tandem MS, Marfey’s, and genomic analyses.
- Design, Synthesis, and Antifungal Activity of 3-substituted-2(5H)-OxaborolesCampbell, Rose; Buchbinder, Nicklas W. ; Szwetkowski, Connor; Zhu, Yumeng; Piedl, Karla; Truong, Mindy; Matson, John B.; Santos, Webster L.; Mevers, Emily (American Chemical Society, 2024-02-22)Next generation antimicrobial therapeutics are desperately needed as new pathogens with multiple resistance mechanisms continually emerge. Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. Herein, we report the antimicrobial properties of 3-substituted-2(5H)-oxaboroles, an unstudied family of medicinally relevant oxaboroles. Our results revealed minimum inhibitory concentrations as low as 6.25 and 5.20 μg/mL against fungal (e.g., Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) pathogens, respectively. These oxaboroles were nonhemolytic and nontoxic to rat myoblast cells (H9c2). Structure-activity relationship studies suggest that planarity is important for antimicrobial activity, possibly due to the effects of extended conjugation between the oxaborole and benzene rings.
- Discovery of Biofilm Inhibitors from the Microbiota of Marine Egg MassesKyei, Lois; Piedl, Karla; Miller, Eleanor M.; Mevers, Emily (American Chemical Society, 2024-05-30)Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult to treat. In the biofilm state, bacteria are protected against both antibiotics and the host’s immune system; currently, there are no therapeutics that target biofilms. In this study, we screened a chemical fraction library representing the natural product capacity of the microbiota of marine egg masses, namely, the moon snail egg collars. This led to the identification of active fractions targeting both Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Subsequent analysis revealed that a subset of these fractions were capable of eradicating preformed biofilms, all against S. aureus. Bioassay-guided isolation led us to identify pseudochelin A, a known siderophore, as a S. aureus biofilm inhibitor with an IC50 of 88.5 μM. Mass spectrometry-based metabolomic analyses revealed widespread production of pseudochelin A among fractions possessing S. aureus antibiofilm properties. In addition, a key biosynthetic gene involved in producing pseudochelin A was detected on 30% of the moon snail egg collars and pseudochelin A is capable of inhibiting the formation of biofilms (IC50 50.6 μM) produced by ecologically relevant bacterial strains. We propose that pseudochelin A may have a role in shaping the microbiome or protecting the egg collars from microbiofouling.
- The microbiota of moon snail egg collars is shaped by host-specific factorsPiedl, Karla; Aylward, Frank O.; Mevers, Emily (American Society for Microbiology, 2024-10-04)Moon snails (Family: Naticidae) lay eggs using a mixture of mucus and sediment to form an egg mass commonly referred to as an egg collar. These egg collars do not appear to experience micro-biofouling or predation, and this observation led us to hypothesize that the egg collars possess a chemically rich microbiota that protect the egg collars from pathogens. Herein, we sought to gain an understanding of the bacterial composition of egg collars laid by a single species of moon snails, Neverita delessertiana, by amplifying and sequencing the 16S rRNA gene from the egg collar and sediment samples collected at four distinct geographical regions in southwest Florida. Relative abundance and non-metric multidimensional scaling plots revealed distinct differences in the bacterial composition between the egg collar and sediment samples. In addition, the egg collars had a lower α-diversity than the sediment, with specific genera being significantly enriched in the egg collars. Analysis of microorganisms consistent across two seasons suggests that Flavobacteriaceae make up a large portion of the core microbiota (36%-58% of 16S sequences). We also investigated the natural product potential of the egg collar microbiota by sequencing a core biosynthetic gene, the adenylation domains (ADs), within the gene clusters of non-ribosomal peptide synthetase (NRPS). AD sequences matched multiple modules within known NRPS gene clusters, suggesting that these compounds might be produced within the egg collar system. This study lays the foundation for future studies into the ecological role of the moon snail egg collar microbiota. IMPORTANCE Animals commonly partner with microorganisms to accomplish essential tasks, including chemically defending the animal host from predation and/or infections. Understanding animal-microbe partnerships and the molecules used by the microbe to defend the animals from pathogens or predation has the potential to lead to new pharmaceutical agents. However, very few of these systems have been investigated. A particularly interesting system is nutrient-rich marine egg collars, which often lack visible protections, and are hypothesized to harbor beneficial microbes that protect the eggs. In this study, we gained an understanding of the bacterial strains that form the core microbiota of moon snail egg collars and gained a preliminary understanding of their natural product potential. This work lays the foundation for future work to understand the ecological role of the core microbiota and to study the molecules involved in chemically defending the moon snail eggs.