Background/Aims: As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10^-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.

Acinetobacter baumannii is a growing threat, although lytic bacteriophages have been shown to effectively kill A. baumannii. However, the interaction between the host and the phage has not been fully studied. We demonstrate the global profile of transcriptional changes in extensively drug-resistant A. baumannii AB1 and the interaction with phage φAbp1 through RNA sequencing (RNA-seq) and bioinformatic analysis. Only 15.6% (600/3,838) of the genes of the infected host were determined to be differentially expressed genes (DEGs), indicating that only a small part of the bacterial resources was needed for φAbp1 propagation. Contrary to previous similar studies, more upregulated rather than downregulated DEGs were detected. Specifically, φAbp1 infection caused the most extensive impact on host gene expression at 10 min, which was related to the intracellular accumulation phase of virus multiplication. Based on the gene coexpression network, a middle gene (gp34, encoding phage-associated RNA polymerase) showed a negative interaction with numerous host ribosome protein genes. In addition, the gene expression of bacterial virulence/resistance factors was proven to change significantly. This work provides new insights into the interactions of φAbp1 and its host, which contributes to the further understanding of phage therapy, and provides another reference for antibacterial agents. IMPORTANCE Previous research has reported the transcriptomic phage-host interactions in Escherichia coli and Pseudomonas aeruginosa, leading to the detailed discovery of transcriptomic regulations and predictions of specific gene functions. However, a direct relationship between A. baumannii and its phage has not been previously reported, although A. baumannii is becoming a rigorous drug-resistant threat. We analyzed transcriptomic changes after φAbp1 infected its host, extensively drug-resistant (XDR) A. baumannii AB1, and found defense-like responses of the host, step-by-step control by the invader, elaborate interactions between host and phage, and elevated drug resistance gene expressions of AB1 after phage infection. These findings suggest the detailed interactions of A. baumannii and its phage, which may provide both encouraging suggestions for drug design and advice for the clinical use of vital phage particles.

The gastrointestinal microbiome is crucial in human health. With greater than 10 times the cell count of an individual, the gastrointestinal microbiome provides many benefits to the host. It plays an important role in chronic illnesses and immune diseases and also following burns and trauma. This study aimed to determine whether severe burns affect the gastrointestinal microbiome during the early stages of after burn injury and the extent to which the microbiome is disturbed by such burns. We used a rat burn model to investigate any changes occurring in the microbiome after the burn trauma using 16S rRNA sequencing and downstream α-diversity, β-diversity, and taxonomy analysis. With 128631 and 143694 clean sequence reads, an average of 2287 and 2416 operational taxonomic units (OTUs) were recognized before and after the burn injury, respectively. Bacterial diversity within the pre- and post-burn groups was similar according to OTU richness, Chao 1 index, Shannon index and ACE index. However, the constituents of the gastrointestinal microbiota changed after the burn injury. Compared with the pre-burn samples, the post-burn samples showed a tendency to cluster together. The ratio of Firmicutes to Bacteroidetes decreased after the burn injury. Also, the abundance of some probiotic organisms (i.e., butyrate-producing bacteria and Lactobacillus) decreased after the burn injury. In contrast, opportunistic pathogenic bacteria, such as those of the genera Escherichia and Shigella and the phylum of Proteobacteria are more abundant post-burn. In conclusion, dysbiosis in the gastrointestinal microbiome was observed after the burn injury. Although the total number of species in the gastrointestinal microbiome did not differ significantly between the pre- and post-burn injury groups, the abundance of some bacterial components was affected to various extents.