Researchers Identify How S aureus Survives In Bones During Invasive Infection

About 30% of individuals are known to carry Staphylococcus aureus (S aureus) within their noses. Although most of the time these bacteria are not particularly harmful, in health care settings, these bacteria are known to result in several serious, life-threatening infections.

Frequently, invasive S aureus infections will occur in the bone, and oftentimes, prove to be resistant to available treatment, making these infections particularly difficult to treat. At the annual ASM Microbe meeting held in Atlanta, Georgia, researchers from Vanderbilt University Medical Center, report findings from a recent study that sheds light on just how these bacteria are able to survive within the bones.

“We found that S aureus needs to synthesize certain amino acids itself, rather than relying on host nutrients,” lead author of the study Jim Cassatt, MD, PhD, associate director of the Vanderbilt Institute for Infection, Immunology, and Inflammation, said in a recent statement.

To come to these findings, they looked at how S aureus obtains cellular building blocks from the host. In order to power cellular proliferation and form various macromolecules such as proteins, nucleic acids, and lipids, 13 essential metabolites are needed; this is true across all forms of life.

“Because these particular amino acid biosynthesis pathways are found only in microbes and plants, they might be particularly attractive targets for the development of new antimicrobial compounds,” Dr Cassat explained.

One of the sites that are most frequently targeted by S aureus during invasive infection is the bone. Bone infections (osteomyelitis) are not particularly responsive to antimicrobial therapy, many individuals with these infections often undergo surgeries to remove infected or damaged bones. Dr Cassat’s lab focuses on understanding how pathogens are able to survive in bone and how cells within the bone detect or respond to these pathogens.

For this study, his team wanted to test how a specific pathogen, S aureus, acquired critical nutrients during invasive infection of the bone. To do this, they used a large panel of bacterial mutants deficient in several metabolic pathways. By putting the mutants in a murine osteomyelitis model, investigators sought to identify the pathways that contribute to pathogen survival within the bone. The team also created an ex vivo assay to support this research, in which Staph was forced to use the bone as its sole source of crucial nutrients. They found that specific metabolic pathways were critical for bacterial survival within the bone.

Previous to this, Dr Cassat and his team were using “transposon sequencing” (TnSeq) to detect S aureus genes that were thought to contribute to osteomyelitis. However, they found that with this approach it was difficult to identify which metabolic pathways were important for bone infection.