MbShea@PWP@English@UMCP

ABSTRACT: This literature review explores the characteristics of the staphylococcal superantigen-like proteins, with emphasis on staphylococcal superantigen-like proteins SSL3 and SSL4. The superantigen-like proteins are derived from the staphylococcal superantigens and are known to cause inflammatory immune responses. The superantigen-like proteins, on the other hand, do not possess this property and many are characterized as immune evasion proteins. There are currently fourteen characterized SSLs, which are thought to reside on two distinct operons in the staphylococcal genome. SSL3 and SSL4 have been characterized specifically as immune evasion proteins that inhibit TLR2 binding of lipopeptides in the human body. TLR2 binding and activation is crucial in effecting downstream pathways involved in the innate immune response. The effects of SSL3 and SSL4 have been demonstrated in vivo to increase the virulence of the S. aureus infection in murine models. Additionally, although SSL3 strongly binds and inhibits TLR2 and SSL4 has a weak binding affinity for TLR2, hybrid and variant proteins in some strains have been characterized to exhibit differential binding patterns. These hybrid and variant proteins are not extensively characterized in the literature, but enough evidence exists to suggests that they could potentially be targeted as part of a therapeutic intervention to treat antibiotic-resistant S. aureus infections, which are increasing in prevalence. Further research into SSL3/4 hybrids and the superantigen-like proteins in general is needed to establish a basis for such treatments in the future.

READER'S PROFILE: I’m writing this response from the perspective of a biologist or healthcare professional who has a basic background in research on S. aureus virulence factors and treatments.

READER'S RESPONSE: I am skeptical on whether this singular set of proteins is worth investigating and has a significant clinical effect on the course of S. aureus infection. Specifically, this literature review focuses on SSL3 and SSL4, but doesn’t emphasize the effects of the other SSLs which could be just as important. Even though there are murine models demonstrating a significant effect of these proteins on S. aureus virulence, this effect may not translate over into human S. aureus infection. I agree that further research is needed into this protein set to determine whether they are clinically significant and worth researching as a potential therapeutic target for S. aureus treatment, or if efforts would better be directed elsewhere. While I think this research may be promising, there is not enough knowledge on the subject to start calling SSL3 and SSL4 potential therapeutic targets for clinical intervention.

Suggestions for myself: In my literature review, I should emphasize the current research showing the extent to which these proteins influence S. aureus virulence and the importance of the TLR2 response pathway.

REVISED THESIS OR PROBLEM STATEMENT: Although the premise of my general problem statement has not changed, as I discussed with you earlier, I could potentially make it more of a thesis-driven literature review with a thesis focused on investigating the properties of SSL3 and SSL4.

VOICE: same throughout – the voice will be relatively scientific and as neutral as I can make it so I don’t misrepresent facts or details.

CITATION: mostly natural language citations throughout document as I invoke articles and then describe them.

Y, I think your citation will be more formal (author, date) but check with me about this internal guidance document for research.

About your reluctant reader: I think the most important lesson here is that we have competing targets for research priority. If, eventually, your protein target class is not fruitful, then, you will need research humility to pause and rethink. The same is true for your reader. I am excited that you are at a near threshold in targets. Be sure to stay on this research question, if only to check the lit. Let me know later on.

For example, I worked on amino acids in space (moon rock residues). I have been happy to follow some of this research now for more than 36 years!