This may be a difficult problem to define as cellulitis isn't a very specific condition. The more obvious symptoms associated with cellulitis (redness, swelling and such) are largely mediated by the immune response so they don't necessarily require any toxins to be involved. Sometimes it just takes a few pathogen-associated molecular patterns (PAMPs - see the first link). That being said, alpha toxin also seems to make a major contribution to infections like cellulitis (see second link).

http://www.pnas.org/content/103/37/13831.full

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075103

Dear colleague Derek, I agree with colleague J. Harry Caufield from Virginia Commonwealth University, that this may be a difficult problem to define as cellulitis isn't a very specific condition. The more obvious symptoms associated with cellulitis (redness, swelling and such) are largely mediated by the immune response so they don't necessarily require any toxins to be involved. I think that alpha toxin also seems to make a major contribution to infections like cellulitis.

cellulitis due to inflammation can be cuase by S.aureus cysteine protease staphopain B but also needed contribution of serine protease for activation. Staphopain B by activating chemerin elicit and maintain chronic inflammation. Here is a reference of Kuling P 

Staphylococcus aureus-derived staphopain B, a potent cysteine protease activator of plasma chemerin.

Kulig P1, Zabel BA, Dubin G, Allen SJ, Ohyama T, Potempa J, Handel TM, Butcher EC, Cichy J.

Thank you Mr. (Dr.) Caufield, Dr. Styriak and (Dr./Prof.) Qureshi, - I greatly appreciate your responses to my question. I will definitely be looking into all these aspects of Staph in much greater detail: A-TOXIN, and STAPHOPAIN B. (S.aureus cysteine protease staphopain B is a totally new avenue for me to look at - thanks!)

Given that Staph seems to evade the immune system for a while in cellulitis and is not a well-confined infection (compared to boils, pimples, folliculitis, abscesses, etc.) I tend to speculate that things like STAPHYLOKINASE might also be more implicated.

FYI, another aspect that interests me greatly is the work of Dr. Primrose Freestone, a microbial endocrinologist, who has shown that Staph is extremely responsive to reading our stress hormones (norepinephrine) as a cue for growth and virulence changes. I think this is when, where and how the bacteria develops its varying techniques for invasion.

I hope I can call on you to check my further speculations. Thanks again.

Staphylococcus aureus can produce several toxins, some of which contribute to invasion and survival of the organism in the tissues. More specific in the dermatological context are the exfoliative toxins (epidermolytic toxins ET-A and ET-B) responsible for the generalized staphylococcal scalded skin syndrome (SSSS) and bullous impetigo. The superantigen toxic shock syndrome toxin 1 (TSST-1), and probably other toxins, are involved in toxic shock syndrome. Staphylococcal scarlatina is thought to be mediated by staphylococcal erythrogenic toxin or other byproducts of the organism . Superantigens from S. aureus may also affect the evolution of atopic dermatitis. Staphylococcal cell-wall products (teichoic acid, peptidoglycan and protein A), exert many effects on the host immune system . Protein A may be involved in adherence of the bacterium to the host cell, and it can bind to the Fc portion of IgG in addition to the specific Fab fragment of IgE . In cellulitis (as opposed to erysipelas), Staphylococcus aureus is occasionally implicated alone or together with a Streptococcus. Staphylococcus aureus is occasionally isolated from lesions of erysipelas. Staphylococcus aureus should be regarded as an occasional cause of cellulitis, but rarely if at all of classical erysipelas.

Dear Prof./Dr. Bashir

Thank you very very much for this description, and please accept my apologies for replying so late. Your write-up is extremely useful to me and has filled in many of the gaps in my knowledge of Staph's toxins. You have also helped me with defining the differences between cellulitis and erysipelas. (The cases I am dealing with definitely have Staph involvement.)

With regards to cellulitis, I have begun looking at it from a different angle. This was driven by certain questions: 1] why certain people are particularly vulnerable to cellulitis and Staph, 2] why it occurs primarily on the lower legs, 3] why it does not spread to the other parts of the body, and 4] why it is not contagious.

Slowly, I came to the conclusion that the illness rather revolves around the host and their defences. This came after reading about the findings of Dr. Richard Gallo (dermatologist) and his colleagues regarding rosacea. In that illness it is strongly speculated that the cathelicidins (LL-37) have been altered to a more pro-inflammatory and angiogenic/neovascular role, rather than their usual role as a cationic antimicrobial peptide (cAMP).

These pro-inflammatory changes to LL-37 involve excess KLK5, too much Vit D in its 1,25(OH)2D3 format, too much IL-17 coming from Th17 or γδ-T cells, and the activation of TLR2 (via Staph's LTA), NOD2 (via Staph's Peptidoglycan) or NALP3 (via Staph's α-toxin) which have been hypersensitized through NF-κB transcription to produce too many cytokines. The further activation of FPRL1 (possibly via Staph's δ-hemolysin toxin) may also play a role in changing LL-37 to a more neovascular role, as well as FPRL1 activating SAA's (serum amyloid A's) chemotactic ability and possibly SAA's stimulation of IL-23, resulting in yet more Th17 cells and too much IL-17.

The above is my "work-in-progress" theory about the immunology involved, but the bottom line is that cellulitis, in my view, is likely to be a typical auto-inflammatory illness (i.e. Th17 driven) with very strong bacterial influences. It is along those lines I have tried certain alternative remedies that so far appear to have worked.

Your mentioning of Staph Protein A (SpA) is of great interest to me. Its adherence to IgG and IgE is something I know little about. Can you direct me to the best papers on this topic? What I know so far is that our immune system responds to SpA quite uniquely - it ignores all other toxins. In effect, SpA gives our immune system "tunnel vision" or employs a "invasion by distraction" strategy. SpA also interacts directly with TNFR1 (common in airway epithelia), where it activates IL-4 causing Th2 cell proliferation, with obvious IgE and IL-5 responses, and subsequent eosinophilia (hence the atopic readings seen in atopic dermatitis and asthma too). I believe that Staph's Enterotoxin B (SEB) also activates an IL-4 response. This appears to me to be "invasion by dis-information" where our immune system misreads these two toxins and instead gears up for an incorrect invader (i.e. eosinophils being for parasites).

Dear Townshend 

Hope you find a satisfactory informations in the following references:

* Ginsburg CM. Staphylococcal toxin syndromes. Pediatr Infect Dis J 1991; 10:

319–21.

* Chen W-Y, Sager S, Tung E et al. Human peripheral blood lymphocyte

activation by protein A from Staphylococcus aureus. Infect Immun 1982; 36:

59–65.

* Neuber K, Konig W. Effects of Staphylococcus aureus cell wall products (teichoic

acid, peptidoglycan) and enterotoxin B on immunoglobulin (IgE, IgA,

IgG) synthesis and CD23 expression in patients with atopic dermatitis.

Immunology 1992; 75: 23–8.

* Dahl MV. Staphylococcus aureus and atopic dermatitis. Arch Dermatol 1983;

119: 840–6.

* Friedmann SJ, Schroeter AL, Homburger HA. IgE antibodies to Staphylococcus

aureus. Arch Dermatol 1985; 121: 869–72