Comments for:

Antimicrobial proteins

Submitter: Charles J. Diskin | Hndt512@directvinternet.com

Hypertension,Nephrology, Dialysis,Transplantation, Auburn University, 121 N. 20th S,Opelika AL 36801

Published April 8, 2002

My congratulations to Tomas for an excellent review of an exciting subject. We found a similar bactericidal activity to protein in ascitic fluid over twenty years ago.1 Up until that time it was felt that spontaneous bacterial peritonitis occurred due to the fact that ascites was a good culture medium that promoted growth of bacteria. To the contrary, we found that it had a bactericidal activity that disappeared as the protein concentration decreased. Our findings were confirmed later that decade.2 We had correlated the protein concentration of ascites to complement levels. We had assumed that although the two were correlated well together, and to the bactericidal ability, that the decreased bactericidal effect resulted from decreased complement activity whose production decreased in tandem with albumin as liver function deteriorated. Tomas’ group has brilliantly shown that there is another explanation, namely, that of the ability polyvalent polypeptides to alter availability of circulating ions. We have described the ability of he counter-ion cloud that surrounds albumin to affect other physiologic functions such as its effect on entropy, oncotic pressure and edema,3,4 and on urine surface tension with consequent bubble formation.5 Like Tomas, we feel that this offers an exciting possible opportunity for the use of polyvalent macromolecules to perhaps alter availability of circulating divalent cations through electrostatic attachment to the counterion cloud in biologic fluids such as peritoneal dialysate and thereby improve antimicrobial activity which would reduce the most distressing cause of morbidity in that type of dialysis treatment, namely, peritonitis. Unfortunately, we have found the opposite effect.6 The fresh fluid entering the peritoneal cavity, which contained 3.5 meq/L of calcium and 1.5 meq/L of magnesium ions, was able to kill up to 1 million colonies/ cc of coagulase negative staphylococcus; however, the effect was abolished when human albumin or serum were added. The addition of these polyelectrolyte colloids should have trapped some of the calcium and magnesium ions in its counterion cloud, but resulted in loss rather than enhancement of antimicrobial activity. The effect occurred both in vitro and also usualy occurred with spent dialysis which had accumulated protein naturally during the treatment process itself, although the antimicrobial effect was maintained in the few who exhibited little protein loss into their dialysate. Similar to Tomas, we also showed that the antimicrobial effect was not merely due to the inability of the dialysate to provide nutrients since the same bacteria grew exceedingly well in the veronal buffer used as a control. The tests were performed on acellular fluid so as to avoid confusion with the later reported deleterious effects of the fresh dialysate on numerous leukocyte functions. Obviously to be truly effective in a clinical setting the any salubrious effect on an acellular fluid, would need to outweigh its inimical effects on non-bacterial cellular function.
In summary, like Tomas and Cole, we have found a salubrious effect of protein on the bactericidal activity of ascites, but a deleterious effect of that same protein on antimicrobial activity of dialysate. Perhaps, a solution to this enigma could result in resolution of the great bane of peritoneal dialysis.
1. Diskin CJ, Ho G: The protective effect of protein and complement in ascitic fluid. RI Med J 1981;64:521-525.
2. Runyon BA. Low protein concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis. Gastroenterology 1986;91:1343-6.
3. Diskin CJ, Gupta RB, Ravis W et al. Edema, Oncotic pressure and entropy: novel considerations for the treatment of edema through attention to thermodynamics. Nephron 1998;78:131-138.
4. Diskin CJ, Stokes TJ, Dansby LM, Carter TB, Radcliff L, Thomas SG. Towards an understanding of oedema. BMJ 1999;318:1610-13.
5. Diskin CJ, Stokes TJ, Dansby LM, Carter TB, Radcliff L. Surface tension, proteinuria and the urine bubbles of Hippocrates. Lancet 2000;355:901-902.
6. Diskin CJ, Coplon NS, Feldman C, Vosti K. Antimicrobial activity in continuous ambulatory peritoneal dialysis. Perit Dial Bull 1983;3:150-154.