bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.03.14.584828

Assessing horizontal gene transfer in the rhizosphere of Brachypodium distachyon using fabricated ecosystems (EcoFABs)

Abstract

Horizontal gene transfer (HGT) is a major process by which genes are transferred within microbes in the rhizosphere. However, examining HGT remains challenging due to the complexity of mimicking conditions within the rhizosphere. Fabricated ecosystems (EcoFABs) have been used to investigate several complex processes in plant associated environments. Here we show that EcoFABs are efficient tools to examine and measure HGT frequency in the rhizosphere. We provided the first demonstration of gene transfer via triparental conjugation system in the Brachypodium distachyon rhizosphere in the EcoFABs using Pseudomonas putida KT2440 as both donor and recipient bacterial strain with the donor having the mobilizable and non-self-transmissible plasmid. We also observed that the frequency of conjugal plasmid transfer in the rhizosphere is potentially dependent on the plant developmental stage, and composition and amount of root exudates. The frequency of conjugation also increased with higher numbers of donor cells. We have also shown the transfer of plasmid from P. putida to another B. distachyon root colonizer, Burkholderia sp. showing the possibility of HGT within a rhizosphere microbial community. Environmental stresses also influence the rate of HGT in the rhizosphere between species and genera. Additionally, we observed transfer of a non-self transmissible donor plasmid without the helper strain on agar plates when supplemented with environmental stressors, indicating reduced dependency on the helper plasmid under certain conditions. This study provides a robust workflow to evaluate conjugal transfer of engineered plasmids in the rhizosphere when such plasmids are introduced in a field or plant associated environment. ImportanceWe report the use of EcoFABs to investigate the HGT process in a rhizosphere environment. It highlights the potential of EcoFABs in recapitulating the dynamic rhizosphere conditions as well as their versatility in studying plant-microbial interactions. This study also emphasizes the importance of studying the parameters impacting the HGT frequency. Several factors such as plant developmental stages, nutrient conditions, number of donor cells and environmental stresses influence gene transfer within the rhizosphere microbial community. This study paves the way for future investigations into understanding the fate and movement of engineered plasmids in a field environment.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Priya, S., Rossbach, S., Eng, T., Andeer, P., Lin, H.-H., Mortimer, J., Northen, T., Mukhopadhyay, A.. 2024-03-14. Assessing horizontal gene transfer in the rhizosphere of Brachypodium distachyon using fabricated ecosystems (EcoFABs). https://doi.org/10.1101/2024.03.14.584828

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

KEEP EXPLORING

Related preprints

pTRIP, a novel integration plasmid for Listeria monocytogenes

In the past decades, several tools to genetically modify the human pathogen Listeria monocytogenes were developed. Here, we constructed a new integrative plasmid system for L. monocytogenes named pTRIP, for treB insertion plasmid. pTRIP is a vector which stably integrates into the treB locus of the wild type EGD-e. This locus encodes the sole trehalose-specific EIIB and EIIC component of a phosphotransferase system. Successful integration leads to the disruption of treB and thus, to an inability of the resulting L. monocytogenes strains to grow on trehalose as sole carbon source. Due to integration through double homologous recombination, it is the first integrative system which does not require antibiotic selection pressure. To assess functionality of the pTRIP system, prfA and its native promoter region were integrated into the treB locus of a {Delta}prfA strain. Complementation was confirmed in 78% of the isolated clones, indicating successful integration of prfA into the treB locus. We further constructed derivatives of pTRIP harboring the constitutive Pp60 (pTRIP1) and the inducible Prha (pTRIP2) promoter to further expand application possibilities. Microscopic analyses confirmed the functionality of both promoter constructs and showed dose-dependent induction for Prha. pTRIP is an efficient tool for stable gene expression as well as functional studies and expands genetic modification possibilities for L. monocytogenes.

microbiology↗

A rational design strategy and validation for protease-resistant fusion-inhibitor antiviral peptides

Peptide-based fusion inhibitors are promising pharmaceuticals in the fight against enveloped viruses relying on membrane fusion for host infection. However, peptide therapeutic applications have long been hindered by their poor stability in vivo. Here, we discovered that peptide inhibitors with the wildtype sequence of the heptad repeat 2 (HR2) domain of the SARS-CoV-2 spike protein are efficiently cleaved by Transmembrane Protease, Serine 2 (TMPRSS2), a key protease involved in the SARS-CoV-2 virus-cell fusion pathway. We then identified the corresponding cleavage sites and designed three protease-resistant peptides using ranking based on deep mutational scanning and natural occurrence. The three candidates all exhibit inhibitory activity in a cell-cell fusion assay. A high-resolution cryo-EM structure of the top candidate, HR2-NHN, bound to its HR1 target reveals the molecular basis for its potent activity. The top candidate of the cell-based screening assay significantly improved efficacy relative to the wildtype peptide when administered 12 h before infection in both an authentic virus-cell infection assay and a mouse assay. More broadly, our results suggest that the design strategies for protease-resistant peptides could be applied to a broad spectrum of other enveloped viruses and pave the way for the development of safe, prophylactic antivirals that can be administered before exposure.

microbiology↗

Host soluble inositol phosphate signaling promotes coronavirus replication

Coronaviruses rely extensively on host pathways for replication, making host-directed therapies an attractive strategy for broad-spectrum antivirals with reduced risk of viral resistance. Here we identify the host soluble inositol phosphate pathway as a previously unrecognized dependency for coronavirus infection. Genetic or pharmacologic inhibition of several kinases in this pathway markedly suppresses replication of both alpha- and betacoronaviruses, while increasing pathway activity promotes viral replication. We developed UNC7844, a potent multi-target inhibitor of these kinases, which reduces coronavirus replication by more than four orders of magnitude in cultured cells and suppresses coronavirus infection in mice. Mechanistically, UNC7844 suppresses inositol (pyro)phosphates production, disrupts phosphoinositide homeostasis, and impairs late endosomal dynamics, blocking early post-entry steps required for viral genome release and replication. Together, our findings establish the soluble inositol (pyro)phosphate pathway as an important regulator of coronavirus infection and highlight its inhibition as a promising host-directed antiviral strategy.

microbiology↗