Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1″-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, ERC-AdG GA 101018520 Israel Science Foundation, MAPATS grant 2720/22 Deutsche Forschungsgemeinschaft, SPP 2330, grant 464312965 Minerva Foundation with funding from the Federal German Ministry for Education and Research research grant from Magnus Konow in honor of his mother Olga Konow Rappaport Ministry of Aliyah and Immigrant Absorption, https://ror.org/05aycsg86 Clore Scholars Program

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

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Covering: 2005 to July 2025Methicillin-resistant Staphylococcus aureus (MRSA), emerging as one of the most common multidrug-resistant (MDR) bacterial strains, has posed a serious threat to global heal...

Yoshioka et al. show that bacteria wrap their flagella to squeeze through near cell-width confinements, which allows symbiotic microbes to navigate constricted gut regions within insect hosts.

Light-driven enzymatic catalysis has enabled important abiological transformations in vitro. Now a cellular ene-reductase photoenzyme is integrated with a de novo-designed olefin biosynthetic pathway ...

Purpose This review aims to provide an overview of current knowledge on the involvement of QS in phage infection. The role of QS in bacterial defence against phages is emphasized, without overlooking ...

Scientific Reports - The Lysis cassette of jumbophage PhiKZ

PhD Project - Nutrient uptake in commensal bacteria: exploring uncharacterised TonB-dependent transporters. at Newcastle University, listed on FindAPhD.com

Bacteriophages and PICIs spread bacterial defenses via lateral transduction, shaping microbial immunity and pathogen evolution.

In this study, the authors identify and structurally characterize a single-component anti-phage defense system named CMoRE (Cytosine Modification Restriction Endonuclease).

Background Microcins are small antibacterial proteins secreted by gram-negative bacteria. The activities of new microcins discovered using bioinformatic searches need to be validated and characterized to understand how they mediate competition in microbiomes and to evaluate their potential as new therapeutics for combating antibiotic resistance. Engineered plasmids containing the type I secretion system associated with Escherichia coli Microcin V (MccV) can secrete heterologous proteins, including other class II microcins, and this system functions in other bacterial hosts. However, existing microcin secretion constructs are not designed for easily swapping components — such as origins of replication, resistance genes, promoters, and signal peptides — that may need to be changed for compatibility with other chassis. Results We refactored the E. coli MccV type I secretion system into genetic parts compatible with a modular Golden Gate assembly scheme and used these parts to construct two-plasmid microcin secretion systems. In our design, one plasmid encodes the type I secretion system proteins, and the other encodes a signal peptide fused to the cargo protein that will be secreted. We tested two versions of a system with inducible promoters separately controlling expression of the components on each plasmid. One used plasmids that replicate in E. coli and its close relatives. The other used broad-host-range plasmids. When induced to secrete MccV, both versions produced similar zones of inhibition against a susceptible strain of E. coli . Next, we identified putative class II microcins in genomes of bacteria from plant-associated genera ( Pantoea , Erwinia , and Xanthomonas ) using an existing bioinformatics pipeline. We screened 23 of these putative microcins for E. coli self-inhibition. Seven exhibited some inhibition, mostly later in growth curves, but none had effects that were comparable in strength to MccV. Conclusions The genetic parts we created can be assembled in various combinations into tailored systems for secreting small proteins from diverse bacterial chassis. These systems can be used to further characterize the targets of novel microcins and to secrete these or other small proteins for various applications. For example, beneficial bacteria used in crop protection could be engineered to secrete microcins that kill or inhibit plant pathogens to increase their efficacy. ### Competing Interest Statement JKP is a co-inventor on patent application US-20250340892-A1 (Gram-Negative Bacteria Containing Peptide Secretion System). United States Army Research Office, W911NF-20-1-0195 U.S. National Science Foundation, IOS-2103208 United States Department of Agriculture, 2024-67013-42304

A small team of volunteers is tracking thousands of falsified studies, including cases of bribery, fraud and plagiarism

Rice is a global staple crop that is susceptible to various pathogens, including Pseudomonas fuscovaginae, causing sheath brown rot, and Rhizoctonia solani AG 1-IA, which causes sheath blight. Notably...

Abstract. We have evaluated the prediction accuracy of three different tools, deep-learning-based AlphaFold2, AlphaFold3, and large language model-based ES

Albumin selectively inhibits Mucorales growth through the release of bound free fatty acids.

Some microbes externalize costly biosynthetic precursors in sufficient quantities to sustain a recipient population through cross-feeding. However, it is unclear whether metabolites are externalized purely for a reciprocal benefit or if metabolite externalization also plays a physiological role for the producer. Here we focus on adenine, a metabolite externalized by some strains of the phototrophic bacterium Rhodopseudomonas palustris at sufficient levels to support Escherichia coli growth. In 10 long-term monocultures and 22 cocultures pairing R. palustris with E. coli, extracellular adenine externalized by all 140 isolates screened was 1.7 - 3.4-fold higher than that by the ancestor, suggesting that there was selective pressure for adenine externalization. We hypothesized that adenine is toxic to R. palustris. The CGA0092 growth rate decreased by half in the presence of about 0.3 mM external adenine. This inhibitory effect increased by an order of magnitude when we over-expressed adenine phosphoribosyltransferase to overcome a bottleneck in the purine salvage pathway, suggesting that toxicity stems from a metabolite derived from adenine. To assess whether adenine tolerance is connected to adenine externalization, we surveyed 12 evolved isolates and 49 environmental strains that externalized different levels of adenine, revealing a significant positive correlation. Our data suggests a physiological role for externalization of costly-metabolites like adenine at the origin of cross-feeding. In addition to cross-feeding, resulting metabolic interactions could be negative, considering that even a biosynthetic precursor like adenine can be inhibitory. ### Competing Interest Statement The authors have declared no competing interest. United States Army Research Office, https://ror.org/05epdh915, W911NF-14-1-0411, W911NF-17-1-0159 U.S. National Science Foundation, MCB-1749489

A library of 400 phage protein-coding genes is used to find a trove of antiphage systems, revealing systems that target tail fibre and major capsid proteins.