C. acnes central nervous system catheter infection induces long-term changes in the CSF proteome.

Cutibacterium acnes (C. acnes) is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is likely underdiagnosed due to the difficulty in culturing this pathogen. Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. Currently the gold standard for identifying CSF shunt infections is microbiologic culture. However, C. acnes infection often results in falsely negative cultures; therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a rat model of CSF catheter infection to C. acnes. We found elevated levels of IL-1β, IL-6, CCL2 and IL-10 in the CSF and brain tissues of animals implanted with C. acnes-infected catheters compared to sterile controls at day 1 post-infection. This coincided with modest increases in neutrophils in the CSF and to a greater extent the brain tissue of animals with C. acnes infection, which closely mirrors the clinical findings in patients with C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of disease, typified at day 1 post-infection by an acute phase and pathogen neutralization response evolving to a response consistent with wound resolution at day 28, compared to sterile catheter placement. Collectively, these results demonstrate that it is possible to distinguish C. acnes infection from sterile post-operative inflammation and CSF proteins could be useful in a diagnostic strategy for this pathogen that is difficult to diagnose.