Brooks S, Weaver JA, Klomchit A, Alharthi SA, Onlamun T, Nurani R, Vong TK, Alberti F and Greco C

Endophytic fungi constitute a rich source of secondary metabolites that can be manipulated to produce desirable novel analogs for combating current agricultural challenges for crop production, especially controlling plant disease. The endophytic fungus Daldinia eschscholtzii MFLUCC 19-0629, was newly isolated from tropical ancient plants, Oncosperma sp., and displays a broad-spectrum of antifungal and antibacterial activities against several plant pathogens. The discovery that D. eschscholtzii MFLUCC 19-0629 has a broad spectrum of antimicrobial activity against seven major plant pathogenic microorganisms relevant to crop production and its complete genome sequence carries immense importance in the advancement of novel microbial biocontrol agents (MBCAs). This also unveils the prospect of uncovering new compounds that could be utilized for sustainable agriculture and pharmaceutical purposes.

Frontiers in Chemical Biology. March 2024

Javier Sánchez Romano, Jaione Simón-Santamaria, Peter McCourt, Bård Smedsrød, Kim Erlend Mortensen, Antonia P. Sagona, Karen Kristine Sørensen, Anett Kristin Larsen

Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1F^gfp) in mice. The results presented herein contribute to increased knowledge about the pharmacokinetics of the T7-like phage K1F in the mammalian system. The cell types of the liver that are responsible for rapid phage blood clearance are identified. Our results highlight the need for more research about appropriate dose regimens when phage therapy is delivered intravenously and advise essential knowledge about cell systems that should be investigated further for detailed phage pharmacodynamics.

mSphere. February 2024

Huba L Marton, Apoorva Bhatt, Antonia P Sagona, Peter Kilbride, Matthew I Gibson

Bacteriophages have many biotechnological and therapeutic applications, but as with other biologics, cryopreservation is essential for storage and distribution. Macromolecular cryoprotectants are emerging for a range of biologics, but the chemical space for polymer-mediated phage cryopreservation has not been explored. Here we screen the cryoprotective effect of a panel of polymers against five distinct phages, showing that nearly all the tested polymers provide a benefit. This work shows that phages are amenable to protection with hydrophilic polymers and opens up new opportunities for advanced formulations for future phage therapies and to take advantage of the additional functionality brought by the polymers.

Biomacromolecules. December 2023

Jack Butler, Nicholas Dale

Connexin32 (Cx32) is expressed in myelinating Schwann cells. It forms both reflexive gap junctions, to facilitate transfer of molecules from the outer to the inner myelin layers and hemichannels at the paranode to permit action potential-evoked release of ATP into the extracellular space. Loss of function mutations in Cx32 cause X-linked Charcot Marie Tooth disease (CMTX), a slowly developing peripheral neuropathy. The mechanistic links between Cx32 mutations and CMTX are not well understood. As Cx32 hemichannels can be opened by increases in PCO₂, we have examined whether CMTX mutations alter this CO₂ sensitivity. We have shown that Schwannoma RT4 D6P2T cells can release ATP in response to elevated PCO₂ via the opening of Cx32. This is consistent with the hypothesis that the CO₂ sensitivity of Cx32 may be important for maintenance of healthy myelin. Our data, showing a transdominant effect of certain CMTX mutations on CO₂ sensitivity, may need to be taken into account in any future gene therapies for this condition.

Frontiers in Cellular Neuroscience. December 2023

María Florencia Mammarella, Leandro Lucero, Nosheen Hussain, Aitor Muñoz-Lopez, Ying Huang, Lucia Ferrero, Guadalupe L Fernandez-Milmanda, Pablo Manavella, Moussa Benhamed, Martin Crespi, Carlos L Ballare, Jose Gutierrez-Marcos, Pilar Cubas, Federico Ariel

The long noncoding RNA (lncRNA) AUXIN-REGULATED PROMOTER LOOP (APOLO) recognizes a subset of target loci across the Arabidopsis thaliana genome by forming RNA–DNA hybrids (R-loops) and modulating local three-dimensional chromatin conformation. Here, we show that APOLO regulates shade avoidance syndrome by dynamically modulating expression of key factors. We show that direct application of APOLO RNA to leaves results in a rapid increase in auxin signaling that is associated with changes in the plant response to far-red light. Collectively, our data support the view that lncRNAs coordinate shade avoidance syndrome in A. thaliana, and reveal their potential as exogenous bioactive molecules. Deploying exogenous RNAs that modulate plant–environment interactions may therefore become a new tool for sustainable agriculture.

EMBO Journal. December 2023

Emily Skates, Hadrien Delattre, Zoe Schofield, Munehiro Asally, Orkun S. Soyer

Recently, the fluorescent benzothiazole dye thioflavin T (ThT) was shown to indicate membrane potential in bacteria due to its cationic nature. This finding prompted a question whether ThT fluorescence is linked to the membrane potential in mammalian cells, which would be important for appropriate utilization of ThT in research and diagnosis. Here, we show that ThT localizes into the mitochondria of HeLa cells in a membrane-potential-dependent manner. The results show that ThT can act as a mitochondrial membrane potential indicator in mammalian cells, when used at low concentrations and with low blue light exposure. However, it causes dissipation of the mitochondrial membrane potential depending additively on its concentrations and blue light exposure. This conclusion motivates a re-evaluation of ThT’s use at micromolar range in live-cell analyses and indicates that this dye can enable future studies on the potential connections between mitochondrial membrane potential dynamics and protein aggregation.

Biophysical Reports. December 2023