Science Seen: Tackling S. aureus by eavesdropping on infections

S. aureus vaccine messenger RNA transcriptome
This messenger RNA ‘heat map,’ generated from 50 patient samples, shows potential target proteins for a more effective S. aureus vaccine. The color scale indicates the magnitude of the transcription level, with red highest.

Staphylococcus aureus causes 11,000 deaths annually in the U.S. alone and is frequently antibiotic-resistant. It’s a leading cause of pneumonia, bloodstream infections, bone/joint infections and surgical site infections and the #1 cause of skin and soft tissue infections. Efforts to develop an S. aureus vaccine have so far failed: the vaccines don’t seem to be capturing the right ingredients to make people immune.

Kristin Moffitt, MD, in Boston Children’s Hospital’s Division of Infectious Diseases, took a step back and asked: “What proteins does S. aureus need to make to establish infection?” The answer, she reasoned, could point to new antigens to include in a vaccine.

The above image shows an early result from Moffitt’s investigation. It’s a “heat map” of the messenger RNA signature — a snapshot of the proteins S. aureus is potentially up-regulating during infection.

An S. aureus ‘hit list’

Moffitt generated the map by testing abscess fluid from 50 children with S. aureus soft tissue infections. She used special probes to look for matches with a panel of 192 proteins believed to be secreted or expressed on the bacterium’s surface, based on genomic sequencing data. The mRNA transcriptome was remarkably consistent across S. aureus strains. It was also similar to that in mouse S. aureus soft tissue infections. However, many of the transcripts appear to be unique to human infection.

Together with critical care physician-researcher Adrienne Randolph, MD, Moffitt and colleagues have also begun testing deep respiratory aspirates from children with severe pneumonia caused by S. aureus. Looking at the most strongly-implicated bacterial transcripts from the abscess samples and a preliminary group of the pneumonia samples, they identified 10 potential proteins that are uniquely up-regulated in each type of infection, and 31 that are up-regulated in both types of infection.

Moffitt will eventually test selected proteins as potential vaccine components in mouse models of S. aureus soft tissue abscess and pneumonia. Her work is being supported by the NIH/NIAID and Boston Children’s Translational Research Program.