Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1987 Sep;55(9):2268–2273. doi: 10.1128/iai.55.9.2268-2273.1987

Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis.

D W Scheifele, G L Bjornson, R A Dyer, J E Dimmick
PMCID: PMC260689  PMID: 3623702

Abstract

Necrotizing enterocolitis (NEC) is a serious neonatal disorder of uncertain cause, although fecal bacteria have been implicated in some outbreaks. We examined coagulase-negative staphylococci (CONS) as possible etiologic agents. In our unit, CONS colonized the bowels of most infants studied, including 46% of 70 NEC cases (mean concentration, 10(9.1) CFU/g of stool). Over 90% of tested isolates produced a hemolysin resembling delta toxin of Staphylococcus aureus. Toxin purified from a NEC-associated isolate of Staphylococcus epidermidis resembled reference delta toxin from S. aureus in size, biologic properties, and antigenicity. This delta-like toxin was enteropathic, causing mucosal necrosis and hemorrhage in injected loops of the bowels of infant rats. Adjacent, nonexposed bowel remained normal, as did loops injected with lecithin-neutralized toxin. Using a new enzyme-linked immunosorbent assay (ELISA), we detected delta-like toxin in the stools of 11 of 35 infants colonized with CONS positive for delta-like toxin (Tox+). Positive tests were strongly associated with NEC. Of 18 cases with Tox+ CONS, 10 were positive (56%), whereas only 1 of 17 control infants so colonized was positive (6%, P = 0.002). In NEC patients, the mean fecal toxin concentration was 1,012 ng/g. Toxicity to fibroblasts was demonstrable in filtrates of each of six ELISA-positive samples tested but was absent in all five ELISA-negative samples tested. We conclude that delta-like toxin is elaborated in the bowels of some infants with Tox+ CONS, and its association with NEC suggests that such CONS are enteropathic. In our unit, this mechanism was apparent in 23% of 44 recent cases of endemic NEC.

Full text

PDF
2271

Images in this article

2271Image
on p.2271

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. L., Collin M. F., O'Keefe J. P., Challapalli M., Myers T. F., Caldwell C. C., Ahmed G. S. A widespread epidemic of mild necrotizing enterocolitis of unknown cause. Am J Dis Child. 1984 Oct;138(10):979–983. doi: 10.1001/archpedi.1984.02140480081025. [DOI] [PubMed] [Google Scholar]
  2. Arvidson S., Holme T., Wadström T. Influence of cultivation conditions on the production of extracellular proteins by Staphylococcus aureus. Acta Pathol Microbiol Scand B Microbiol Immunol. 1971;79(3):399–405. doi: 10.1111/j.1699-0463.1971.tb00079.x. [DOI] [PubMed] [Google Scholar]
  3. Bell M. J., Ternberg J. L., Feigin R. D., Keating J. P., Marshall R., Barton L., Brotherton T. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978 Jan;187(1):1–7. doi: 10.1097/00000658-197801000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blakey J. L., Lubitz L., Barnes G. L., Bishop R. F., Campbell N. T., Gillam G. L. Development of gut colonisation in pre-term neonates. J Med Microbiol. 1982 Nov;15(4):519–529. doi: 10.1099/00222615-15-4-519. [DOI] [PubMed] [Google Scholar]
  5. Chang T. W., Lauermann M., Bartlett J. G. Cytotoxicity assay in antibiotic-associated colitis. J Infect Dis. 1979 Nov;140(5):765–770. doi: 10.1093/infdis/140.5.765. [DOI] [PubMed] [Google Scholar]
  6. Donahue J. A. Antistaphylococcal hemolysins and delta hemolysin inhibitor in adult human serum. Can J Microbiol. 1969 Aug;15(8):957–959. doi: 10.1139/m69-167. [DOI] [PubMed] [Google Scholar]
  7. Fitton J. E., Dell A., Shaw W. V. The amino acid sequence of the delta haemolysin of Staphylococcus aureus. FEBS Lett. 1980 Jun 30;115(2):209–212. doi: 10.1016/0014-5793(80)81170-7. [DOI] [PubMed] [Google Scholar]
  8. Freer J. H., Arbuthnott J. P. Toxins of Staphylococcus aureus. Pharmacol Ther. 1982;19(1):55–106. doi: 10.1016/0163-7258(82)90042-0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gruskay J. A., Abbasi S., Anday E., Baumgart S., Gerdes J. Staphylococcus epidermidis-associated enterocolitis. J Pediatr. 1986 Sep;109(3):520–524. doi: 10.1016/s0022-3476(86)80135-4. [DOI] [PubMed] [Google Scholar]
  11. Heatley N. G. A new method for the preparation and some properties of staphylococcal delta-haemolysin. J Gen Microbiol. 1971 Dec;69(2):269–278. doi: 10.1099/00221287-69-2-269. [DOI] [PubMed] [Google Scholar]
  12. Heatley N. G. Production of antibody to staphylococcal delta-haemolysin in the rabbit. Br J Exp Pathol. 1977 Aug;58(4):400–411. [PMC free article] [PubMed] [Google Scholar]
  13. Kapral F. A. Inhibition of Staphylococcus aureus delta hemolysin by phospholipids. Proc Soc Exp Biol Med. 1972 Nov;141(2):519–521. doi: 10.3181/00379727-141-36812. [DOI] [PubMed] [Google Scholar]
  14. Kapral F. A. Staphylococcus aureus delta toxin as an enterotoxin. Ciba Found Symp. 1985;112:215–229. doi: 10.1002/9780470720936.ch12. [DOI] [PubMed] [Google Scholar]
  15. Kleck J. L., Donahue J. A. Production of thermostable hemolysin by cultures of Staphylococcus epidermidis. J Infect Dis. 1968 Jun;118(3):317–323. doi: 10.1093/infdis/118.3.317. [DOI] [PubMed] [Google Scholar]
  16. Kliegman R. M., Fanaroff A. A. Necrotizing enterocolitis. N Engl J Med. 1984 Apr 26;310(17):1093–1103. doi: 10.1056/NEJM198404263101707. [DOI] [PubMed] [Google Scholar]
  17. Kosloske A. M. Pathogenesis and prevention of necrotizing enterocolitis: a hypothesis based on personal observation and a review of the literature. Pediatrics. 1984 Dec;74(6):1086–1092. [PubMed] [Google Scholar]
  18. Kreger A. S., Kim K. S., Zaboretzky F., Bernheimer A. W. Purification and properties of staphylococcal delta hemolysin. Infect Immun. 1971 Mar;3(3):449–465. doi: 10.1128/iai.3.3.449-465.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lawrence G., Bates J., Gaul A. Pathogenesis of neonatal necrotising enterocolitis. Lancet. 1982 Jan 16;1(8264):137–139. doi: 10.1016/s0140-6736(82)90383-x. [DOI] [PubMed] [Google Scholar]
  20. Mahajan V. M., Reddy T. N., Agarwal L. P. Toxigenic strains of Staphylococcus epidermidis and their experimental corneal pathogenicity in rabbits. Int Ophthalmol. 1982 Nov;5(3):155–161. doi: 10.1007/BF00149145. [DOI] [PubMed] [Google Scholar]
  21. Nolte F. S., Kapral F. A. Hydrophobic interaction chromatography of Staphylococcus aureus delta-toxin. Infect Immun. 1981 Mar;31(3):1094–1098. doi: 10.1128/iai.31.3.1094-1098.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. O'Brien A. D., Kapral F. A. Increased cyclic adenosine 3',5'-monophosphate content in guinea pig ileum after exposure to Staphylococcus aureus delta-toxin. Infect Immun. 1976 Jan;13(1):152–162. doi: 10.1128/iai.13.1.152-162.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rotbart H. A., Levin M. J. How contagious is necrotizing enterocolitis? Pediatr Infect Dis. 1983 Sep-Oct;2(5):406–413. doi: 10.1097/00006454-198309000-00019. [DOI] [PubMed] [Google Scholar]
  24. Smith G. M., Shaw W. V. Comparison of three methods for the purification of the delta haemolysin of Staphylococcus aureus. J Gen Microbiol. 1981 Jun;124(2):365–374. doi: 10.1099/00221287-124-2-365. [DOI] [PubMed] [Google Scholar]
  25. Stephan W., Róka L. Adsorption von Lipoproteiden. Behandlung von Seren mit Adsorbentien. I. Z Klin Chem Klin Biochem. 1968 May;6(3):186–190. [PubMed] [Google Scholar]
  26. Turner W. H., Pickard D. J. Immunological relationship between delta-hemolysins of Staphylococcus aureus and coagulase-negative strains of staphylococci. Infect Immun. 1979 Mar;23(3):910–911. doi: 10.1128/iai.23.3.910-911.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Westra-Meijer C. M., Degener J. E., Dzoljic-Danilovic G., Michel M. F., Mettau J. W. Quantitative study of the aerobic and anaerobic faecal flora in neonatal necrotising enterocolitis. Arch Dis Child. 1983 Jul;58(7):523–528. doi: 10.1136/adc.58.7.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yoshioka H., Iseki K., Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics. 1983 Sep;72(3):317–321. [PubMed] [Google Scholar]
  29. Yu V. Y., Joseph R., Bajuk B., Orgill A., Astbury J. Necrotizing enterocolitis in very low birthweight infants: a four-year experience. Aust Paediatr J. 1984 Mar;20(1):29–33. doi: 10.1111/j.1440-1754.1984.tb00032.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES