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From the Gut to the Brain: Transcriptomic Insights into Neonatal Meningitis Escherichia coli Across Diverse Host Niches

ABSTRACT: Neonatal meningitis caused by Escherichia coli (NMEC) is a leading cause of morbidity and mortality in newborns, and its pathogenesis relies on the ability of the bacterium to adapt and survive in diverse host environments. Despite advances in neonatal care, significant gaps remain in our understanding of how NMEC reprogram their transcriptome to survive in physiologically relevant niches. This study investigated the transcriptomic profiles of E. coli strain RS218 (O18:H7:K1) in four under host-relevant environment —colonic fluid (CF), serum (S), human brain endothelial cells (HBECs) and cerebrospinal fluid (CSF)—to mimic the infection landscape of neonatal meningitis. High-throughput RNA sequencing (RNA-seq) was performed to profile NMEC’s transcriptomic responses in each niche, and differential gene expression analyses were conducted to identify enriched pathways.

ORGANISM(S): Escherichia coli

PROVIDER: GSE291265 | GEO | 2025/03/11

REPOSITORIES: GEO

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Project description:Meningitis is a life-threatening condition characterized by the inflammation of the leptomeningeal membranes surrounding the brain and spinal cord. The term meningitis is an umbrella term and includes several different etiologies. The majorities of meningitis cases are caused by viruses (viral meningitis; VM) and are often associated with low mortality rates and low risk of developing neurological. In contrast, meningitis caused by some viral infections, such as tick-borne encephalitis (TBE), can be life-threatening when left untreated with increased risk of developing neurological sequelae. Acute bacterial meningitis (ABM), however, is one of the leading causes of death due to infectious diseases worldwide and is associated with rapid disease progression, high mortality rates and increased risk of long-term neurological sequelae in survivors. As meningitis is caused by numerous different pathogens, the host-response is typically highly variable and it is currently unknown if different pathogens can introduce specific proteome changes in the cerebrospinal fluid (CSF). In this study we applied DIA-MS to provide novel insights for in-depth understanding of central nervous system functioning and host response during meningitis in a cohort of patients with differential diagnosis of meningitis, to account for variability contributed by different disease-causing pathogens. The results reveal drastic changes in the CSF proteome during meningitis, where in particular a massive increase of neutrophil derived proteins in the CSF correlated with ABM, suggesting that activated neutrophils play a particular role in ABM. Additionally both ABM and VM result in marked reduction of brain-specific proteins in the CSF, which could be indicative of pathophysiological mechanisms leading to brain damage. Furthermore, generation of lasso regression model enables separation of ABM with high sensitivity and specificity, demonstrating that several proteins are required to confidently discriminate between ABM, VM and BM.

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From the Gut to the Brain: Transcriptomic Insights into Neonatal Meningitis Escherichia coli Across Diverse Host Niches

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