A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2',3'-cGAMP and activates the effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides and induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether bacteria harboring CBASS antagonize and co-evolve with phages is unknown. Here, we identified an endogenous cGAS-like enzyme in Pseudomonas aeruginosa that generates 3',3'-cGAMP during phage infection, signals to a phospholipase effector, and limits phage replication. In response, phages express an anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity. Acb2 also binds to molecules produced by other bacterial cGAS-like enzymes (3',3'-cUU/UA/UG/AA) and mammalian cGAS (2',3'-cGAMP), suggesting broad inhibition of cGAS-based immunity. Upon Acb2 deletion, CBASS blocks lytic phage replication and lysogenic induction, but rare phages evade CBASS through major capsid gene mutations. Altogether, we demonstrate endogenous CBASS anti-phage function and strategies of CBASS inhibition and evasion.

Photosynthesis converts solar energy into chemical energy to sustain all life on earth by providing oxygen and food, and controlling the atmospheric carbon dioxide. During this process, the water-splitting and oxygen-evolving reaction is catalyzed by photosystem II (PSII), while photosystem I (PSI) generates the reducing power for the reduction of NADP⁺ to NADPH. Together with their peripheral light-harvesting complexes (LHCs), photosystems function as multisubunit supercomplexes located in the thylakoid membranes of cyanobacteria, algae, and plants. Recent advances in single-particle cryo-electron microscopy (cryoEM), X-ray free electron laser (XFEL) and other techniques have revealed unprecedented structural and catalytic details concerning the two supercomplexes. Several high-resolution structures of the complexes from plants were solved, and serial time-resolved crystallography and “radiation-damage-free” femtosecond XFEL also provided important insights into the mechanism of water oxidation. Here, we review these exciting advances in the studies of the photosystem supercomplexes with an emphasis on PSII-LHCII, propose presently unresolved problems in this field, and suggest potential tendencies for future studies.

The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences and are typically small, creating a challenge to detect anti-defense homologs across prokaryotic and phage genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired sequence. Here, we developed ‘AntiDefenseFinder’—a free open-source tool and web service that detects 156 anti-defense systems of one or more proteins in any genomic sequence. Using this dataset, we identified 47 981 anti-defense systems distributed across prokaryotes and their viruses. We found that some genes co-localize in ‘anti-defense islands’, including Escherichia coli T4 and Lambda phages, although many appear standalone. Eighty-nine per cent anti-defense systems localize only or preferentially in MGE. However, >80% of anti-Pycsar protein 1 (Apyc1) resides in nonmobile regions of bacterial genomes. Evolutionary analysis and biochemical experiments revealed that Apyc1 likely originated in bacteria to regulate cyclic nucleotide (cNMP) signaling, but phage co-opted Apyc1 to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions and a deeper understanding of host–pathogen arms race.

Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 °C) to that of the PET hydrolase FAST-PETase (67.80 °C) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.

Phages and their bacterial hosts together constitute a vast and diverse ecosystem. Facing the infection of phages, prokaryotes have evolved a wide range of antiviral mechanisms, and phages in turn have adopted multiple tactics to circumvent or subvert these mechanisms to survive. An in-depth investigation into the interaction between phages and bacteria not only provides new insight into the ancient coevolutionary conflict between them but also produces precision biotechnological tools based on anti-phage systems. Moreover, a more complete understanding of their interaction is also critical for the phage-based antibacterial measures. Compared to the bacterial antiviral mechanisms, studies into counter-defense strategies adopted by phages have been a little slow, but have also achieved important advances in recent years. In this review, we highlight the numerous intracellular immune systems of bacteria as well as the countermeasures employed by phages, with an emphasis on the bacteriophage strategies in response to host antiviral immunity.