Staphylococcus epidermidis phage activates metabolic and biosynthetic processes in stationary cells

Abstract

Background In nature, bacteria are frequently found in the stationary state of growth. The efficacy of antimicrobials, including phages, against these low-metabolic activity cells is usually limited. The Staphylococcus epidermidis SEP1 phage was previously shown to reduce the numbers of stationary cells. This study analysed for the first time how both exponential and stationary cells responded to phage infection using an RNA-seq approach.

Materials Exponential and stationary cultures of S. epidermidis were infected with SEP1. RNA was extracted from samples collected shortly before and after infection (5/15/30 min) and the transcriptomes analysed by RNA-seq.

Results In exponential cells, at 5 min post-infection, only 3 genes of a bacterial defence system involved in DNA modification were upregulated. However, upregulation of the restriction endonuclease gene, necessary for cleavage of phage DNA by the host, was not observed, with the phage being able to successfully replicate. Stationary cells responded to phage infection by upregulating 29 genes at 5 min post-infection, with this value largely increasing for 894 at 15 min. Functional enrichment analysis showed an overrepresentation of genes involved in translation and RNA metabolic processes, particularly nucleobase-containing compound biosynthetic processes, and ribonucleoside and purine biosynthetic processes. Numerous gene ontology terms were enriched, including 35 biological processes, 19 molecular functions and 5 cellular components, demonstrating that several genes involved in different metabolic and biosynthetic processes were highly expressed in phage-infected stationary cells.

Conclusions SEP1 successfully hijacks the transcription machinery of its host, activating important metabolic and biosynthetic processes in stationary cells necessary for its effective replication. The gathered data would provide valuable insights for a better implementation of phage therapy since phages with ability to infect stationary cells could be more efficient in the treatment of infections, but also for the activation of their metabolic activity and consequent resensitization to commonly used antibiotics.