Abstract
Bacterial products from gram-positive bacteria, such as peptidoglycan, teichoic acid, and toxins, activate mononuclear cells to produce tumor necrosis factor alpha (TNF). The present study evaluated the release of soluble cell wall components from Staphylococcus epidermidis capable of inducing TNF after exposure of the bacteria to various antibiotics. A clinical S. epidermidis isolate (694) was incubated with either penicillin, oxacillin, vancomycin, or clindamycin at five times the MIC. Supernatants of the cultures obtained by filtration were added to plastic adherent monocytes in the absence or presence of human serum. After 18 h of incubation, monocyte supernatants were tested for the presence of TNF by enzyme-linked immunosorbent assay (ELISA). Supernatants from bacteria incubated with beta-lactam antibiotics induced higher TNF levels than those obtained from bacteria incubated with culture medium only (no antibiotics), vancomycin, or clindamycin. Human serum potentiated supernatant-induced TNF release, especially in beta-lactam supernatants. The soluble peptidoglycan and teichoic acid contents of supernatants, as estimated by inhibition ELISA and, for peptidoglycan, also by affinity depletion with vancomycin-Sepharose gel, were proportional to TNF release. Differences in the ability of individual antibiotics to generate TNF-releasing products from S. epidermidis were observed, the most potent antibiotics being penicillin and oxacillin.
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- Bhakdi S., Klonisch T., Nuber P., Fischer W. Stimulation of monokine production by lipoteichoic acids. Infect Immun. 1991 Dec;59(12):4614–4620. doi: 10.1128/iai.59.12.4614-4620.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bhakdi S., Muhly M., Korom S., Hugo F. Release of interleukin-1 beta associated with potent cytocidal action of staphylococcal alpha-toxin on human monocytes. Infect Immun. 1989 Nov;57(11):3512–3519. doi: 10.1128/iai.57.11.3512-3519.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bone R. C. The pathogenesis of sepsis. Ann Intern Med. 1991 Sep 15;115(6):457–469. doi: 10.7326/0003-4819-115-6-457. [DOI] [PubMed] [Google Scholar]
- Burchard K. W., Minor L. B., Slotman G. J., Gann D. S. Staphylococcus epidermidis sepsis in surgical patients. Arch Surg. 1984 Jan;119(1):96–100. doi: 10.1001/archsurg.1984.01390130078014. [DOI] [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Crowder J. G., White A. Teichoic acid antibodies in staphylococcal and nonstaphylococcal endocarditis. Ann Intern Med. 1972 Jul;77(1):87–90. doi: 10.7326/0003-4819-77-1-87. [DOI] [PubMed] [Google Scholar]
- Eykyn S. J. Staphylococcal sepsis. The changing pattern of disease and therapy. Lancet. 1988 Jan 16;1(8577):100–104. doi: 10.1016/s0140-6736(88)90294-2. [DOI] [PubMed] [Google Scholar]
- Gemmell C. G., Thelestam M. Toxinogenicity of clinical isolates of coagulase-negative staphylococci towards various animal cells. Acta Pathol Microbiol Scand B. 1981 Dec;89(6):417–421. [PubMed] [Google Scholar]
- Gold M. R., Miller C. L., Mishell R. I. Soluble non-cross-linked peptidoglycan polymers stimulate monocyte-macrophage inflammatory functions. Infect Immun. 1985 Sep;49(3):731–741. doi: 10.1128/iai.49.3.731-741.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg M. E., Djavadi-Ohaniance L. Methods for measurement of antibody/antigen affinity based on ELISA and RIA. Curr Opin Immunol. 1993 Apr;5(2):278–281. doi: 10.1016/0952-7915(93)90018-n. [DOI] [PubMed] [Google Scholar]
- Heumann D., Barras C., Severin A., Glauser M. P., Tomasz A. Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun. 1994 Jul;62(7):2715–2721. doi: 10.1128/iai.62.7.2715-2721.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Issekutz A. C. Removal of gram-negative endotoxin from solutions by affinity chromatography. J Immunol Methods. 1983 Jul 29;61(3):275–281. doi: 10.1016/0022-1759(83)90221-1. [DOI] [PubMed] [Google Scholar]
- Kernodle D. S., McGraw P. A., Barg N. L., Menzies B. E., Voladri R. K., Harshman S. Growth of Staphylococcus aureus with nafcillin in vitro induces alpha-toxin production and increases the lethal activity of sterile broth filtrates in a murine model. J Infect Dis. 1995 Aug;172(2):410–419. doi: 10.1093/infdis/172.2.410. [DOI] [PubMed] [Google Scholar]
- Leeson M. C., Fujihara Y., Morrison D. C. Evidence for lipopolysaccharide as the predominant proinflammatory mediator in supernatants of antibiotic-treated bacteria. Infect Immun. 1994 Nov;62(11):4975–4980. doi: 10.1128/iai.62.11.4975-4980.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin M. A., Pfaller M. A., Wenzel R. P. Coagulase-negative staphylococcal bacteremia. Mortality and hospital stay. Ann Intern Med. 1989 Jan 1;110(1):9–16. doi: 10.7326/0003-4819-110-1-9. [DOI] [PubMed] [Google Scholar]
- Mattsson E., Rollof J., Verhoef J., Van Dijk H., Fleer A. Serum-induced potentiation of tumor necrosis factor alpha production by human monocytes in response to staphylococcal peptidoglycan: involvement of different serum factors. Infect Immun. 1994 Sep;62(9):3837–3843. doi: 10.1128/iai.62.9.3837-3843.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mattsson E., Van Dijk H., Van Kessel K., Verhoef J., Fleer A., Rollof J. Intracellular pathways involved in tumor necrosis factor-alpha release by human monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan are partly similar. J Infect Dis. 1996 Jan;173(1):212–218. doi: 10.1093/infdis/173.1.212. [DOI] [PubMed] [Google Scholar]
- Mattsson E., Verhage L., Rollof J., Fleer A., Verhoef J., van Dijk H. Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. FEMS Immunol Med Microbiol. 1993 Oct;7(3):281–287. doi: 10.1111/j.1574-695X.1993.tb00409.x. [DOI] [PubMed] [Google Scholar]
- Mirelman D., Bracha R., Sharon N. Penicillin-induced secretion of soluble, uncross-linked peptidoglycan by Micrococcus luteus cells. Biochemistry. 1974 Nov 19;13(24):5045–5053. doi: 10.1021/bi00721a028. [DOI] [PubMed] [Google Scholar]
- Parsonnet J., Gillis Z. A. Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. J Infect Dis. 1988 Nov;158(5):1026–1033. doi: 10.1093/infdis/158.5.1026. [DOI] [PubMed] [Google Scholar]
- Peterson P. K., Wilkinson B. J., Kim Y., Schmeling D., Douglas S. D., Quie P. G., Verhoef J. The key role of peptidoglycan in the opsonization of Staphylococcus aureus. J Clin Invest. 1978 Mar;61(3):597–609. doi: 10.1172/JCI108971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeffer K., Matsuyama T., Kündig T. M., Wakeham A., Kishihara K., Shahinian A., Wiegmann K., Ohashi P. S., Krönke M., Mak T. W. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993 May 7;73(3):457–467. doi: 10.1016/0092-8674(93)90134-c. [DOI] [PubMed] [Google Scholar]
- Ponce de Leon S., Wenzel R. P. Hospital-acquired bloodstream infections with Staphylococcus epidermidis. Review of 100 cases. Am J Med. 1984 Oct;77(4):639–644. doi: 10.1016/0002-9343(84)90354-1. [DOI] [PubMed] [Google Scholar]
- Prins J. M., Kuijper E. J., Mevissen M. L., Speelman P., van Deventer S. J. Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. Infect Immun. 1995 Jun;63(6):2236–2242. doi: 10.1128/iai.63.6.2236-2242.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabin R. L., Bieber M. M., Teng N. N. Lipopolysaccharide and peptidoglycan share binding sites on human peripheral blood monocytes. J Infect Dis. 1993 Jul;168(1):135–142. doi: 10.1093/infdis/168.1.135. [DOI] [PubMed] [Google Scholar]
- Raynor R. H., Scott D. F., Best G. K. Oxacillin-induced lysis of Staphylococcus aureus. Antimicrob Agents Chemother. 1979 Aug;16(2):134–140. doi: 10.1128/aac.16.2.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rotta J. Endotoxin-like properties of the peptidoglycan. Z Immunitatsforsch Exp Klin Immunol. 1975 Jul;149(2-4):230–244. [PubMed] [Google Scholar]
- Simon D. M., Koenig G., Trenholme G. M. Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli. J Infect Dis. 1991 Oct;164(4):800–802. doi: 10.1093/infdis/164.4.800. [DOI] [PubMed] [Google Scholar]
- Tracey K. J., Lowry S. F., Cerami A. Cachectin: a hormone that triggers acute shock and chronic cachexia. J Infect Dis. 1988 Mar;157(3):413–420. doi: 10.1093/infdis/157.3.413. [DOI] [PubMed] [Google Scholar]
- Vaudaux P., Grau G. E., Huggler E., Schumacher-Perdreau F., Fiedler F., Waldvogel F. A., Lew D. P. Contribution of tumor necrosis factor to host defense against staphylococci in a guinea pig model of foreign body infections. J Infect Dis. 1992 Jul;166(1):58–64. doi: 10.1093/infdis/166.1.58. [DOI] [PubMed] [Google Scholar]
- Wakabayashi G., Gelfand J. A., Jung W. K., Connolly R. J., Burke J. F., Dinarello C. A. Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. J Clin Invest. 1991 Jun;87(6):1925–1935. doi: 10.1172/JCI115218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wecke J., Johannsen L., Giesbrecht P. Reduction of wall degradability of clindamycin-treated staphylococci within macrophages. Infect Immun. 1990 Jan;58(1):197–204. doi: 10.1128/iai.58.1.197-204.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weidemann B., Brade H., Rietschel E. T., Dziarski R., Bazil V., Kusumoto S., Flad H. D., Ulmer A. J. Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect Immun. 1994 Nov;62(11):4709–4715. doi: 10.1128/iai.62.11.4709-4715.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wheat L. J., Wilkinson B. J., Kohler R. B., White A. C. Antibody response to peptidoglycan during staphylococcal infections. J Infect Dis. 1983 Jan;147(1):16–22. doi: 10.1093/infdis/147.1.16. [DOI] [PubMed] [Google Scholar]
- Zeiger A. R., Tuazon C. U., Sheagren J. N. Antibody levels to bacterial peptidoglycan in human sera during the time course of endocarditis and bacteremic infections caused by Staphylococcus aureus. Infect Immun. 1981 Sep;33(3):795–800. doi: 10.1128/iai.33.3.795-800.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeiger A. R., Wong W., Chatterjee A. N., Young F. E., Tuazon C. U. Evidence for the secretion of soluble peptidoglycans by clinical isolates of Staphylococcus aureus. Infect Immun. 1982 Sep;37(3):1112–1118. doi: 10.1128/iai.37.3.1112-1118.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]