Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates

Background Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. Methods Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. Results We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37 , CSK , MAN2B2 , MGAT1 , MOB3A , MYO9B , SH2D3C , and TEP1 . The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. Conclusions The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK , which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. Impact Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.