Genomic study and lipidomic bioassay of Leeuwenhoekiella parthenopeia: A novel rare biosphere marine bacterium that inhibits tumor cell viability

Abstract

The fraction of low-abundance microbiota in the marine environment is a promising target for discovering new bioactive molecules with pharmaceutical applications. Phenomena in the ocean such as diel vertical migration (DVM) and seasonal dynamic events influence the pattern of diversity of marine bacteria, conditioning the probability of isolation of uncultured bacteria. In this study, we report a new marine bacterium belonging to the rare biosphere, Leeuwenhoekiella parthenopeia sp. nov. Mr9T, which was isolated employing seasonal and diel sampling approaches. Its complete characterization, ecology, biosynthetic gene profiling of the whole genus Leeuwenhoekiella, and bioactivity of its extract on human cells are reported. The phylogenomic and microbial diversity studies demonstrated that this bacterium is a new and rare species, barely representing 0.0029% of the bacterial community in Mediterranean Sea metagenomes. The biosynthetic profiling of species of the genus Leeuwenhoekiella showed nine functionally related gene cluster families (GCF), none were associated with pathways responsible to produce known compounds or registered patents, therefore revealing its potential to synthesize novel bioactive compounds. In vitro screenings of L. parthenopeia Mr9T showed that the total lipid content (lipidome) of the cell membrane reduces the prostatic and brain tumor cell viability with a lower effect on normal cells. The lipidome consisted of sulfobacin A, WB 3559A, WB 3559B, docosenamide, topostin B-567, and unknown compounds. Therefore, the bioactivity could be attributed to any of these individual compounds or due to their synergistic effect. Beyond the rarity and biosynthetic potential of this bacterium, the importance and novelty of this study is the employment of sampling strategies based on ecological factors to reach the hidden microbiota, as well as the use of bacterial membrane constituents as potential novel therapeutics. Our findings open new perspectives on cultivation and the relationship between bacterial biological membrane components and their bioactivity in eukaryotic cells, encouraging similar studies in other members of the rare biosphere.

Biosynthetic gene profiling and genomic potential of the novel photosynthetic marine bacterium Roseibaca domitiana

“…Besides, the exploration of secondary/specialized metabolism combined with phylogenomic and evolutionary studies is shown to be a valuable strategy to assess the biosynthetic potential of new microbial groups, either at the species level or in an overall context. Finally, this and other recent studies (Ramírez-Durán et al, 2021 ; Gattoni et al, 2023 ) show that rare and minority bacteria harbor untapped metabolic potential for synthesizing novel, biotechnologically significant compounds. A good example is the new marine bacterium R. domitiana V10 T , which is theoretically able to produce plant-promoting compounds and antitumor molecules, which merits prioritizing future in vitro studies.…”

“…nov. Given that this strain was isolated from winter nocturnal samples of the coastal surface, while R. ekhonensis was cultured from the depths of a hypersaline lake, the isolation of strain V10 T supports the use of night-time and seasonal sampling as a strategy for the cultivation of new microorganisms, an approach that we successfully used in a previous study and allowed the isolation of Leeuwenhoekiella parthenopeia , a new rare biosphere bacterium that inhibits the proliferation of tumor cells (Gattoni et al, 2023 ).…”

“…In addition to these methods, we have recently proposed the diel and seasonal sampling as a strategy to increase the probability of isolating new marine microorganisms. These studies considered dynamic phenomena, such as diel vertical migration (DVM) and seasonality with the consequent microbial redistribution, allowing the isolation of the new bacterium Leeuwenhoekiella parthenopeia , belonging to the rare biosphere and, interestingly, with the capacity to inhibit the viability of tumor cells in vitro (Gattoni et al, 2023 ).…”

The Marine Bacterial Genus Euzebya Is Distributed Worldwide in Terrestrial Environments: A Review

“…In terms of microbial diversity, the oceans represent the largest biosphere habitat, containing about 70% of the prokaryotic biomass [1]. In recent decades, interest in the bioactive compounds from marine bacteria has grown enormously [2][3][4][5][6][7][8], and many works have focused on rare marine Actinomycetota [9][10][11][12][13]. One of the most intriguing and rare genera of marine Actinomycetota is Euzebya.…”