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Bacteria Commonly Associated with Central Nervous System Catheter Infections Elicit Distinct CSF Proteome Signatures

ABSTRACT: Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long term neurologic consequences like seizures, decreased IQ and impaired school performance. Currently the diagnosis of shunt infection relies on bacterial culture, however, culture is not always accurate especially as these infections are frequently caused by bacteria capable of forming biofilms like Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa and may have very few planktonic bacteria in the CSF to be picked up on culture. Therefore, there is a critical need to identify a new rapid, and accurate method for diagnosis of CSF shunt infection with broad bacterial species coverage to improve the long-term outcomes of children suffering from these infections.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Ishwor Thapa

LAB HEAD: Dr. Gwenn L. Skar

PROVIDER: PXD038238 | Pride | 2023-01-30

REPOSITORIES: Pride

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			Action	DRS
	14Dec21_Skar_109.raw	Raw
	14Dec21_Skar_111.raw	Raw
	14Dec21_Skar_112.raw	Raw
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	14Dec21_Skar_114.raw	Raw

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C. acnes CNS catheter infection elicits modest early inflammatory changes but long term alterations in the CSF proteome

Project description:Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. C. acnes is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is underdiagnosed due to the difficulty in culturing this fastidious, slow growing pathogen. Currently the gold standard for diagnosis of CSF shunt infections is microbiologic culture, however, in the case of C. acnes diagnostic cultures may be falsely negative. Therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a previously published rat model of CSF shunt 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. We found modest increases in neutrophils in the CSF and to a greater extend the brain tissue of animals with C. acnes infection which mirrors the clinical findings in C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of infection with an acute phase and pathogen neutralization response at day 1 post-infection to a more biosynthetic and metabolic response at day 28 post-infection relating to healing. 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.

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Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus

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Value of lipocalin 2 as a potential biomarker for bacterial meningitis

Project description:Objectives: Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome. Methods: We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam. Results: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis), with the sensitivity: 0.88 (95% confident interval (CI): 0.77-0.94), the specificity: 0.91 (95%CI: 0.88-0.94) and the diagnostic odd ratio: 73.8 (95%CI: 31.8-171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93-0.99). Conclusions: Our results suggest that LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections..

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