Host range expansion of Acinetobacter phage vB_Ab4_Hep4 driven by a spontaneous tail tubular mutation.

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the host ranges of phages is beneficial for phage therapy. Multiple studies have identified that phage tail fiber protein mediates the recognition and binding to the host as receptor binding protein in phage infection. However, the tail tubular-dependent host specificity of phages has not been studied well. In this study, we isolated and characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, we identified a spontaneous mutant of the phage, vB_Ab4_Hep4-M, which revealed an expanded host range compared to the wild-type phage. A single mutation of G to C was detected in the gene encoding the phage tail tubular protein B and thus resulted in an aspartate to histidine change. We further demonstrated that the host range expansion of the phage mutant is driven by the spontaneous mutation of guanine to cytosine using expressed tail tubular protein B. Moreover, we established that the bacterial capsule is the receptor for phage Abp4 and Abp4-M by identifying mutant genes in phage-resistant strains. In conclusion, our study provided a detailed description of phage vB_Ab4_Hep4 and revealed the tail tubular-dependent host specificity in A. baumannii phages, which may provide new insights into extending the host ranges of phages by gene-modifying tail tubular proteins.

The Intervention of Probiotics on Type 2 Diabetes Mellitus in Animal Models.

Type 2 diabetes accounts for more than 90% of diabetes patients with the incidence and prevalence continuously rising globally. As a prospective therapy strategy for type 2 diabetes, probiotics have shown beneficial effects both in animal experiments and human clinical trials. This review summarizes the commonly used animal models in probiotic intervention research and presents the evidence and mechanism of diabetes intervention with probiotics in these animal models. Probiotics can help maintain glucose homeostasis, improve lipid metabolism, promote the production of short-chain fatty acids, and reduce inflammatory reactions in animal models. However, the clinical translation of benefits from probiotics is still challenged by intrinsic differences between experimental animal models and humans, and the application of humanized non-rodent diabetic animal models may contribute to the clinical translation of probiotics in the future.

Isolation and characterization of a novel lytic bacteriophage vB_Efm_LG62 infecting Enterococcus faecium.

Enterococcus faecium has been classified as a "high priority" pathogen by the World Health Organization. Enterococcus faecium has rapidly evolved as a global nosocomial pathogen with adaptation to the nosocomial environment and the accumulation of resistance to multiple antibiotics. Phage therapy is considered a promising strategy against difficult-to-treat infections and antimicrobial resistance. In this study, we isolated and characterized a novel virulent bacteriophage, vB_Efm_LG62, that specifically infects multidrug-resistant E. faecium. Morphological observations suggested that the phage has siphovirus morphology, with an optimal multiplicity of infection of 0.001. One-step growth tests revealed that its latent growth was at 20 min, with a burst size of 101 PFU/cell. Phage vB_Efm_LG62 was verified to have a double-stranded genome of 42,236 bp (35.21% GC content), containing 66 predicted coding sequences as determined by whole genomic sequencing. No genes were predicted to have functions associated with virulence factors or antibiotic resistance, indicating that the phage vB_Efm_LG62 has good therapeutic potential. Our isolation and characterization of this highly efficient phage aids in expanding our knowledge of E. faecium-targeting phages, and provides additional options for phage cocktail therapy.

NIR-II Perylene Monoimide-Based Photothermal Agent with Strengthened Donor-Acceptor Conjugation for Deep Orthotopic Glioblastoma Phototheranostics.

Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.