Associate Microbiologist, Department of Medicine
Brigham and Women's Hospital

jhuebner@channing.harvard.edu

Dr. Huebner's primary research project involves the study and characterization of capsular polysaccharides of Enterococcus faecalis and Enterococcus faecium. Enterococci are now the second most common cause of hospital-acquired infection and are especially common in patients receiving immunosuppresive therapy, patients in intensive care, and neonates. In recent years, many strains of enterococci have developed resistance to all known antibiotics, and lethality due to these infections can be up to 100% in certain patient populations. Until recently, it was not appreciated that enterococci, like many other gram-positive bacteria, possess a capsule. Our results clearly showed that enterococci possess an extracellular polysaccharide and that this capsule may be used as a vaccine, offering new options for the treatment of these often untreatable infections. One of these capsular antigens has been shown to be a teichoic acid consisting of a glycerophosphate-glucose backbone substituted with a glucose molecule. We could demonstrate that both E. faecalis and E. faecium strains express this polysaccharide. This antigen is also a target for opsonic antibodies. Mice challenged intravenously with live enterococci showed high levels of bacteria in kidneys, spleens, and livers. However, animals immunized with purified capsular polysaccharide were protected against challenge with a number of E. faecalis strains and vancomycin-resistant E. faecium strains. Rabbit serum raised against the purified capsular polysaccharide reduced bacterial counts in organs of mice as compared with normal rabbit serum or sterile saline and was also effective as a therapeutic reagent in mice when passive therapy was initiated 48 hours after challenge with live bacteria. This antigen can therefore be used to develop active or passive immunotherapy regimens for the treatment and prevention of enterococcal infections in immunocompromised patients. Further understanding of the interaction of these bacteria with the human host defense system will give new insights into how to prevent enterococcal infections.

Muller E, Hubner J, Gutierrez N, Takeda S, Goldmann DA, Pier GB. Isolation and characterization of transposon mutants of Staphylococcus epidermidis deficient in capsular polysaccharide/adhesin and slime. Infect Immun. 1993 Feb;61(2):551-8. [abstract]

Huebner J, Czerwenka W, Gruner E, von Graevenitz A. Shigellemia in AIDS patients: case report and review of the literature. Infection. 1993 Mar-Apr;21(2):122-4. Review. [abstract]

Gruner E, Kropec A, Huebner J, Altwegg M, Daschner F. Ribotyping of Pseudomonas aeruginosa strains isolated from surgical intensive care patients. J Infect Dis. 1993 May;167(5):1216-20. [abstract]

Huebner J, Pier GB, Maslow JN, Muller E, Shiro H, Parent M, Kropec A, Arbeit RD, Goldmann DA. Endemic nosocomial transmission of Staphylococcus epidermidis bacteremia isolates in a neonatal intensive care unit over 10 years. J Infect Dis. 1994 Mar;169(3):526-31. [abstract]

Huebner J, Kropec A. Cross infections due to coagulase-negative staphylococci in high-risk patients. Zentralbl Bakteriol. 1995 Dec;283(2):169-74. Review. [abstract]

McKenney D, Hubner J, Muller E, Wang Y, Goldmann DA, Pier GB. The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect Immun. 1998 Oct;66(10):4711-20. [abstract]

Hoehn T, Huebner J, Paboura E, Krause M, Leititis JU. Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro. Crit Care Med. 1998 Nov;26(11):1857-62. [abstract]

Huebner J, Wang Y, Krueger WA, Madoff LC, Martirosian G, Boisot S, Goldmann DA, Kasper DL, Tzianabos AO, Pier GB. Isolation and chemical characterization of a capsular polysaccharide antigen shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. Infect Immun. 1999 Mar;67(3):1213-9. [abstract]

Huebner J, Goldmann DA. Coagulase-negative staphylococci: role as pathogens. Annu Rev Med. 1999;50:223-36. Review. [abstract]

Wang Y, Huebner J, Tzianabos AO, Martirosian G, Kasper DL, Pier GB. Structure of an antigenic teichoic acid shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. Carbohydr Res. 1999 Mar 31;316(1-4):155-60. [abstract]

Huebner J, Quaas A, Krueger WA, Goldmann DA, Pier GB: Prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide shared among vancomycin-sensitive and -resistant enterococci. Infect Immun 2000 Aug;68(8):4631-6. [abstract]

Harbarth S, Albrich W, Goldmann DA, Huebner J: Control of multiply resistant cocci: do international comparisons help? Lancet Infect Dis 2001 Nov;1(4):251-61. [abstract]