Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphineconjugated catalase (CAT-TCPP). The formed CAT-TCPP/ FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O 2 generation from tumor endogenous H 2 O 2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.

The first step in bacteriophage infection is recognition and binding to the host receptor, which is mediated by the phage receptor binding protein (RBP). Different RBPs can lead to differential host specificity. In many bacteriophages, such as Escherichia coli and Lactococcal phages, RBPs have been identified as the tail fiber or protruding baseplate proteins. However, the tail fiber-dependent host specificity in Pseudomonas aeruginosa phages has not been well studied. This study aimed to identify and investigate the binding specificity of the RBP of P. aeruginosa phages PaP1 and JG004. These two phages share high DNA sequence homology but exhibit different host specificities. A spontaneous mutant phage was isolated and exhibited broader host range compared with the parental phage JG004. Sequencing of its putative tail fiber and baseplate region indicated a single point mutation in ORF84 (a putative tail fiber gene), which resulted in the replacement of a positively charged lysine (K) by an uncharged asparagine (N). We further demonstrated that the replacement of the tail fiber gene (ORF69) of PaP1 with the corresponding gene from phage JG004 resulted in a recombinant phage that displayed altered host specificity. Our study revealed the tail fiber-dependent host specificity in P. aeruginosa phages and provided an effective tool for its alteration. These contributions may have potential value in phage therapy.

We isolated and characterized a new Pseudomonas aeruginosa myovirus named PaP1. The morphology of this phage was visualized by electron microscopy and its genome sequence and ends were determined. Finally, genomic and proteomic analyses were performed. PaP1 has an icosahedral head with an apex diameter of 68–70 nm and a contractile tail with a length of 138–140 nm. The PaP1 genome is a linear dsDNA molecule containing 91,715 base pairs (bp) with a G+C content of 49.36% and 12 tRNA genes. A strategy to identify the genome ends of PaP1 was designed. The genome has a 1190 bp terminal redundancy. PaP1 has 157 open reading frames (ORFs). Of these, 143 proteins are homologs of known proteins, but only 38 could be functionally identified. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance liquid chromatography-mass spectrometry allowed identification of 12 ORFs as structural protein coding genes within the PaP1 genome. Comparative genomic analysis indicated that the Pseudomonas aeruginosa phage PaP1, JG004, PAK_P1 and vB_PaeM_C2-10_Ab1 share great similarity. Besides their similar biological characteristics, the phages contain 123 core genes and have very close phylogenetic relationships, which distinguish them from other known phage genera. We therefore propose that these four phages be classified as PaP1-like phages, a new phage genus of Myoviridae that infects Pseudomonas aeruginosa.

While screening for alternative antibiotics against multidrug-resistant Acinetobacter baumannii, we isolated a virulent A. baumannii bacteriophage Abp1. Transmission electron microscopy revealed that the phage had an icosahedral head with a short tail and should be classified as a member of the Podoviridae family. SDS-PAGE showed that Abp1 contained at least one major and nine minor proteins. In a single-step growth test, we demonstrated that Abp1 had a latent period of 10 min and a burst size of 350. Abp1 also had a relatively narrow host range. The entire genome was sequenced, and the final assembly yielded a 42,185 bp, linear, double-stranded DNA molecule with a G+C content of 39.15 % and containing 54 putative genes. Among these genes, 26 were functionally known, leaving 28 unknown putative genes. Abp1 is a new member of the phiKMV-like virus subgroup of the T7 group; its genome sequence is very similar to that of the A. baumannii phage phiAB1.