Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.10.20.513013

Anticancer and antibacterial activities of secondary bioactive compounds from endosymbiotic bacteria of aphid and their surrounding organisms (predator and protector)

Abstract

Secondary metabolites of bacterial origin are a valuable source of diverse molecules with antibacterial and anticancer activities. In the current study, 10 endosymbiotic bacteria were isolated from aphids, aphid predators and ants. Bacterial strains were identified based on the 16S rRNA gene. Crude extracts were prepared from each isolated bacteria and tested for their antibacterial activities using the disk diffusion method. The extracts of three bacterial species; Planococcus sp, Klebsiella aerogenes, Enterococcus avium from Aphis punicae, Chrysoperia carnea and Tapinoma magnum, respectively were found to have strong antibacterial activities against one or more of the five pathogenic bacteria tested. The inhibition zones ranged from 10.00{+/-} 0.13 to 20.00{+/-} 1.11mm with minimum inhibitory concentration (MIC) values ranged from 0.156 mg/mL to 1.25 mg/mL. The notable antibacterial activity was for the crude extract of K. aerogenes against Klebsiella pneumonia and Escherichia coli at MIC value of 0.156 mg/mL. The cytotoxic activity of the crude extracts varied according to the tested cell line. The most cytotoxic effect was for the extracts of K. aerogenes and E. avium at a concentration of 0.16 mg/mL against lung carcinoma epithelial cells (A549) with cell reduction of 79.4% and 67.2%, respectively. Crude extracts of K. aerogenes and Pantoea agglomerans at a concentration of 0.16 mg/mL showed 69.4% and 67.8% cell reduction against human colon cancer (Hct116), respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of three crude extracts revealed the presence of several bioactive secondary metabolites that have been reported previously to possess antibacterial and anticancer properties. To the best of our knowledge, this is the first study to report the biological activities of endosymbiotic bacteria from aphids, aphid predators and ants. The promising data presented in this study opens a new avenue for alternative drugs to overcome the continuous emergence of multidrug-resistant bacteria and to find alternative drugs for traditional cancer therapies.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Alsufyani, T., Al-Otaibi, N., Alotaibi, N. J., M'sakni, N. H., Alghamdi, E. M.. 2022-10-21. Anticancer and antibacterial activities of secondary bioactive compounds from endosymbiotic bacteria of aphid and their surrounding organisms (predator and protector). https://doi.org/10.1101/2022.10.20.513013

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

aaRSID, an engineered pyrrolysyl-tRNA synthetase platform for multi-probe proximity proteomics

Proximity labeling (PL) methods utilize spatially targeted chemical or enzymatic generation of a diffusible, reactive intermediate to covalently tag neighboring proteins in living systems. Unlike other tools for studying molecular interactions, PL can detect transient protein relationships with high spatial and temporal sensitivity, allowing for insight into their roles in biological processes. However, current enzymatic PL tools, such as TurboID and APEX2, are limited by their substrate structure and chemistry, which can generate significant background and/or perturb cellular physiology. To address these limitations, we have developed aminoacyl-tRNA synthetase ID (aaRSID), a PL tool that leverages an engineered pyrrolysyl tRNA synthetase (PylRS) for proximity labeling of proteins. We chose PylRS because it can catalyze promiscuous lysine labeling in the absence of its cognate tRNA and utilize a variety of non-canonical amino acids (ncAAs) as substrates. Here, we demonstrate aaRSID's intrinsic proximity labeling activity, use directed evolution to improve this activity, and apply the improved mutant (aaRSID-Ma1.3) for subcellular proteomics and multiplexed imaging. Our work establishes aminoacyl-tRNA synthetases as a new PL enzyme class and introduces a versatile chemical platform for developing ncAA-derived probes to map cellular microenvironments, greatly expanding the applications possible of PL technology.

biochemistry↗

Cellular uptake of folate-olaparib conjugates via folate receptor-mediated endocytosis: Potential for selective delivery of DNA damage response inhibitors into tumour cells

The folate receptor (FR) is overexpressed in a range of human tumours including ovarian cancer cells. We propose that the overexpression of the FR on the surface of ovarian tumour cells could be exploited for the selective delivery of a DNA damage response inhibitor (DDRi) in the form of an intact folate drug conjugate (FDC). This approach would improve the therapeutic index of the parent DDRi facilitating combination studies of the DDRi-based FDC with DNA damaging chemotherapy. FR-mediated cellular uptake of the proposed folate drug conjugates is requisite for FDC selective delivery into tumours. In this study, we synthesised a series of olaparib-based folate conjugates that maintained the biochemical PARP1 inhibition associated with olaparib and showed binding affinity for the folate receptor. Significantly, we identified compounds 10b and 11 that selectively enter FR overexpressing tumour cells via folate receptor-mediated endocytosis in their intact form and engage with their target as demonstrated by the potent inhibition of PARylation (KB cells, PARylation IC50 = 5.7 and 3.9 nM; respectively).

biochemistry↗

Architecture and Energy Transfer of the Bacterial Photosynthetic Unit

In phototrophic organisms, pigment-protein membrane complexes are densely packed to form photosynthetic units (PSUs) that capture solar energy and convert it into chemical energy. Although the structures of many individual photosynthetic complexes have been resolved, how they are arranged and interact with others within photosynthetic membranes to enable efficient excitation energy transfer (EET) remains poorly understood. Here, we report cryo-electron microscopy structures of PSU supercomplex assemblies from the phototrophic a-proteobacterium Rhodovulum viride, including an RC-LH1 core associated with one or two peripheral LH2 complexes and a curved LH2 tetramer. These membrane-derived assemblies define the relative positions and orientations of neighboring photosynthetic complexes and place their pigment arrays in proximity across antenna-antenna and antenna-core interfaces. Structure-based simulations identify potential EET pathways within the PSU assemblies and reveal rapid energy transfer across both LH2-LH2 and LH2-LH1 interfaces. Collectively, these findings provide insights into the assembly and structural modularity of bacterial PSUs and elucidate how the lateral organization of membrane protein complexes facilitates efficient energy transfer. This work extends structural studies of bacterial photosynthesis from individual complexes to their native higher-order assembly, providing a framework for understanding how photosynthetic supercomplex organization shapes energy migration and for guiding the design of artificial photosynthesis.

biochemistry↗