Poster Presentation Lorne Infection and Immunity 2022

Identifying novel commensal virulence strategies and their driver during preterm neonatal sepsis (#171)

Isabella Anna Joubert 1 2 3 , Christopher Mullally 1 2 3 , Amy H Lee 4 , Tobias Strunk 2 5 , Andrew Currie 1 2 3
  1. Centre for Molecular Medicine & Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia
  2. Wesfarmers Centre of Vaccines & Infectious Diseases, Perth, Western Australia, Australia
  3. Women's and Infants Research Foundation Laboratory, King Edward Memorial Hospital, Perth, Western Australia, Australia
  4. Simon Fraser University, Vancouver, British Columbia, Canada
  5. Neonatal Directorate, Child and Adolescent Health Service, Perth, Western Australia, Australia

There are >26,000 Australian infants born preterm (<37 weeks GA) each year who account for well over two-thirds of neonatal deaths and one-third of childhood disabilities. Neonatal late-onset sepsis (LOS; onset between 3-28 days postnatally) is a major contributor to this burden, resulting in both immediate and long-term sequelae.  Staphylococcus epidermidis (S. epidermidis) is the predominant sepsis pathogen in preterm infants, accounting for >60% of cases in Australia. S. epidermidis constitutes a major component of the ubiquitous commensal skin and mucous membrane microbiota of all humans, and consistent with commensalism, rarely causes invasive infections in adults or even term infants. It remains unclear, which pathogenic determinants S. epidermidis employs to become invasive pathogens in immunocompromised hosts, such as preterm infants.

For my Ph.D. project, I aim to directly spy on sepsis-causing pathogens during the invasion of the preterm infant host. To achieve this, I am developing a dual RNA-sequencing (dual RNA-seq) protocol and pipeline to simultaneously analyze the gene expression changes occurring in the blood cells of the neonatal host and infecting pathogen during an episode of sepsis.

Currently, I am optimizing a clinically compatible RNA extraction protocol for the sensitive detection of low-abundance bacterial transcripts from human whole blood using a laboratory model of sepsis. I will use this model to define a set of stereotypic and species-specific virulence and host defense genes upregulated during host-pathogen interactions in a pilot cohort of healthy preterm infants, term infants, and adult hosts challenged with the two important sepsis-causing pathogens, S. epidermidis and Staphylococcus aureus (S. aureus). I will then validate my findings by applying dual RNA-seq to a small set of clinical sepsis samples to understand what makes the preterm infant so susceptible to commensal sepsis and set a crucial first step to find new ways to treat and prevent serious infections experienced by the most vulnerable population of infants.