Global Transcriptomic Analysis of the Interactions between Phage φAbp1 and Extensively Drug-Resistant Acinetobacter baumannii

Abstract

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.

Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

“…Similar to other phage-bacterium interaction studies (26,(28)(29)(30)78), we investigated the transcriptional response of E. faecalis during VPE25 infection using a high MOI (MOI, 10) to increase the probability of phage infection and minimize transcriptional noise from uninfected bacterial cells. However, a lower MOI (MOI, 1) is sufficient to alter the expression profile of at least a subset of quorum sensing and T7SS genes (Fig.…”

“…Additionally, the discovery of phage-modulated host pathways could reveal potential therapeutic targets. Our understanding of bacterial cellular responses during phage infection is limited to transcriptomic analyses in Gram-negative bacteria, whereas Gram-positive genera are understudied (26)(27)(28)(29)(30)(31). Therefore, to fill this gap and further define the molecular underpinnings of enterococcal-phage interactions, we have taken a global genomics approach to identify enterococcal factors critical for productive infection by the lytic phage VPE25 (32).…”

Bacteriophage-Insensitive Mutants of Antimicrobial-Resistant Salmonella Enterica are Altered in their Tetracycline Resistance and Virulence in Caco-2 Intestinal Cells

“…In a targeted approach, phages infecting multi-drug resistant Pseudomonas aeruginosa were isolated that utilized multidrug efflux pumps as receptors [17]. Phage-resistant mutants of P. aeruginosa that possessed mutations in these regions subsequently exhibited enhanced susceptibility to several classes of antibiotics, including ceftazidime, ciprofloxacin, tetracycline, and erythromycin, providing evidence of a genetic trade-off as a result of phage infection [17,25].…”

“…It is possible that alterations in transcriptional activity may account for the observed phenotype. For instance, significant (p < 0.05) downregulation of three antibiotic resistance genes were observed by global transcriptomic analysis of multi-drug-resistant Acinetobacter baumanii infected with phage ∂Abp1 [25]. The enhanced expression of efflux pumps in both phage-resistant Campylobacter jejeuni and P. aeruginosa has also been documented [29,30], leading to speculation that efflux pumps and other AMR proteins may have dual roles in phage resistance.…”

Parallel genomics uncover novel enterococcal-bacteriophage interactions

“…Additionally, the discovery of phage-modulated host pathways could reveal potential therapeutic targets. Our understanding of global bacterial cellular responses during phage infection is limited to transcriptomic analyses in Gram-negative bacteria, whereas Gram-positive species are understudied (26–31). Therefore, to fill this gap and further define the molecular underpinnings of enterococcal-phage interactions, we have taken a global genomics approach to identify enterococcal factors critical for productive infection by the lytic phage VPE25 (32).…”