High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis infection

Background Chronic osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. The factors that determine the pathogen’s adaptation and persistence in bone tissue are still not fully understood. The objective of this study was to define the transcriptional adaptation of S. aureus during the acute and chronic phases of osteomyelitis infection. Results RNA-Seq was used to compare the transcriptional profile of S. aureus during the acute (day 7) and chronic (day 28) phases of an experimental murine bone infection to the strain growing exponentially in broth. The data matrix comprised count data across 2503 genes with a total of 264 genes significantly highly expressed by S. aureus during in vivo versus in vitro growth conditions. These genes encoded proteins involved in gluconeogenesis, proteolysis of host proteins, iron acquisition, evasion of the host immune defenses and stress responses. Only 9 genes were significantly highly expressed by S. aureus during the chronic versus acute stage of infection, which include the genes encoding the arginine deiminase (ADI) pathway and those involved in the stringent response. At the regulatory level, sarA/R and saeR/S as well as the small RNA RsaC were predominantly expressed by S. aureus during in vivo infection. Conclusions The transcriptional profile of S. aureus during in vivo infection reflects the bacterial physiological adaptation to the host environment. Interfering with the host-driven adaptive response of S. aureus can represent a novel therapeutic strategy to render the bacteria more susceptible to elimination by the host’s immune system during chronic infection.