Study sheds light on S. aureus virulence factor regulation
Claremont Calif. — September 21, 2018 — Research conducted by Synedgen Inc.’s Senior Scientist and colleagues from the University of Arkansas appears in the Journal of Proteome Research.
Allister J. Loughran, PhD, of Synedgen, and Stephanie D. Byrum, Karen E. Beenken, Lisa M. Orr, Aaron J. Storey, Samuel G. Mackintosh, Ricky D. Edmondson, Alan J. Tackett, and Mark S. Smeltzer from the University of Arkansas for Medical Sciences and Arkansas Children’s Research Institute conducted the research described in Label-free Proteomic Approach to Characterize Protease-dependent and Independent Effects of sarA Inactivation on the Staphylococcus aureus Exoproteome.
Staphylococcus aureus is an opportunistic Gram-positive bacterial species that exists as a commensal in a significant proportion of the healthy population. In individuals with a weakened immune system, the bacteria can become pathogenic and are capable of causing a diverse array of serious infections including pneumonia,sepsis, and osteomyelitis.
S. aureus treatment can be difficult with antibiotic resistance rates among isolates of S. aureus being high, new druggable targets are needed. The Staphylococcal Accessory Regulator (sarA), is one such target. Among other things, sarA regulates the level of proteases, proteins that degrade S. aureus virulence factors such as toxins. Without sarA, the bacteria are weakened and do not cause the same damage to the host.
Since this protein increases the degradation of the bacteria’s own proteins and new proteomic approach was needed to identify proteins that are changed as a result of loss of sarA function. Using an expanded dual proteomics approach, the team measured the abundance of proteins and characterized the exoproteome of wild type bacteria, sarA mutant bacteria and sarA mutants that also do not make the proteases. The analysis allowed for the separation of protein changes into two distinct groups, protease mediated changes and protease independent changes.The dual approach of conventional proteomic profiling and the new approach outlined in this publication, allowed for the identification of unique protein profiles from both methods, which provides for more complete and robust characterization of exoproteomes in the presence of proteases.
“This paper presented a comprehensive and robust method to analyze exoproteomes when endogenous proteases can impact the findings and highlights Allister’s expertise in investigating bacterial pathogenesis and host response,” remarked Synedgen President & COO Shenda Baker PhD.
This study was supported by the National Institutes of Health (R01AI119380, R21DA041822, P20GM121293, UL1TR000039, P20GM103625, S10OD018445 and P20GM103429).
The abstract is available at: https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00288
Synedgen is developing a new class of health care products based on glycomics, a revolutionary approach using glycopolymers to target mucosal and dermal interfaces. Synedgen uses its Glycomics Technology Platform (GTP) to discover and develop ultra-purified glycopolymers that enhance and mimic the innate immune system by targeting the cell surface glycocalyx and mucosal surfaces. Synedgen has successfully leveraged the GTP to develop marketed Prisyna oral care and Synedgen wound care products, as well as SNSP113, which has been licensed to Synspira and is currently in clinical development for the treatment of cystic fibrosis. Synedgen has established research and manufacturing facilities in Claremont, California.