Alternate Therapy

Alternate Therapy

Pseudomonas aeruginosa infection and alternate therapy

The infection of CF patients with alginate producing mucoid strain of P. aeruginosa is rarely eradicated by antibiotics (2, 8). In the hope of finding new and efficacious measures for the treatment of P. aeruginosa pneumonia in CF patients, scientists from Denmark have explored alternative treatments. They found that the immunization with P. aeruginosa vaccines and adjuvants, or the treatment with IFN-g or the Chinese herbal medicine, Daphne giraldii Nitsche, could decrease the inflammatory response and enhance the bacterial clearance in a rat model (4, 5, 6, 10). Recently, they have been having some success exploring the possibility of using the even more popular Chinese herbal supplement, ginseng, which is widely used in China for thousands of years to modulate and the host immune responses (3, 7). As a modulator of the endocrine system and immune system, ginseng has been shown to have some functions in modulating the production of specific antibodies and the functions of phagocytes and natural killer (NK) cells (3, 13). However, while this may help moderate the course of the disease, other approaches are also needed for clarifying the favorite effect of ginseng on bacterial infection.

Recent studies using animal models have shown that ginseng might play a role in enhancing IR and bacterial clearance (9, 11, 12). We are attempting to understand how bacteria respond to ginseng treatment. The discovery and characterization of genes specifically induced in vivo upon infection and/or at a specific stage of the infection will be the next phase in studying bacterial virulence at the molecular level. Genes isolated are most likely to encode virulence-associated factors or products essential for survival, bacterial cell division and multiplication in situ. Identification of these genes is expected to provide new ways of preventing infection, new targets for anti-microbial therapy, as well as new insights into the infection process. All the previous studies involving ginseng and P. aeruginosa infection were focused on how the immune response was modulated during bacterial infection. We will investigate how P. aeruginosa reacts to ginseng treatment at the molecular level. We will attempt to identify novel bacterial antigens that are expressed or repressed during ginseng treatment. We have constructed a set of appropriate isogenic strains containing well-characterized mutations to elucidate the role of alginate genes in P. aeruginosa pathogenesis, and will use them to obtain detailed information regarding the effect of ginseng treatment.

Mathee Publications:

a. Song, Z.J., H. Wu, K. Mathee, N. Høiby, and A. Kharazmi. 2002. Gerimax ginseng regulates both humoral and cellular immunity during chronic Pseudomonas aeruginosa lung infection. Journal of Alternative and Complementary Medicine 8:459-466

Press Releases:

a. Song, Z. J., H. Wu, K. Mathee, N. Hoiby and A. Kharazmi.. 2001. Effects of Gerimax ginseng treatment on the chronic lung infection with mucoid and non-mucoid P. aeruginosa in rats. Abstract selected for Press Release at The 101st Annual Meeting of the American Society for Microbiology. May 20-24th, Orlando. 2001.

b. The media of Denmark, USA, Britain and China reported or highlighted the ginseng research for more than 20 times.

References Cited:

1.
Handfield, M., L. J. Brady, A. Progulske-Fox, and J. D. Hillman. 2000. IVIAT: a novel method to identify microbial genes expressed specifically during human infections. Trends Microbiol 8:336-339.

2.
Høiby, N. 1975. Prevalence of mucoid strains of Pseudomonas aeruginosa in bacteriological specimens from patients with cystic fibrosis and patients with other diseases. Acta Pathol. Microbiol. Scand. Suppl. 83:549-552.

3.
Huang, K. C. 1993. The pharmacology of Chinese herbs. CRC Press, Inc, Boca Raton, Florida.

4.
Johansen, H., F. Espersen, S. J. Cryz, H. Hougen, A. Fomsgaard, J. Rygaard, and N. Høiby. 1994. Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection. Infect Immun 62:3146-3155.

5.
Johansen, H. K., H. P. Hougen, J. S. J. Cryz, J. Rygaard, and N. Høiby. 1995. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats. Am. J. Respir. Crit. Care Med. 152:1337-1346.

6.
Johansen, H. K., H. P. Hougen, J. Rygaard, and N. Høiby. 1996. Interferon-gamma (IFN-g) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats. Clin Exp Immunol 103:212-218.

7.
O'Hara, M., D. Kiefer, K. Farrell, and K. Kemper. 1998. A review of 12 commonly used medicinal herbs. Arch Fam Med 7:523-536.

8.
Pedersen, S. S., H. Moller, F. Espersen, C. H. Sorensen, T. Jensen, and N. Høiby. 1992. Mucosal immunity to Pseudomonas aeruginosa alginate in cystic fibrosis. Acta Pathol Microbiol Scand Suppl 100:326-334.

9.
Song, Z., H. K. Johansen, V. Faber, C. Moser, A. Kharazmi, J. Rygaard, and N. Høiby. 1997. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats. Antimicrob Agents Chemother 41:961-964.

10.
Song, Z., H. K. Johansen, C. Moser, and N. Høiby. 1996. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection. Acta Pathol Microbiol Immunol Scand Suppl 104:350-354.

11.
Song, Z., A. Kharazmi, H. Wu, V. Faber, C. Moser, H. Krogh, J. Rygaard, and N. Høiby. 1998. Effects of ginseng treatment on neutrophil chemiluminescence and immunoglobulin G subclasses in a rat model of chronic Pseudomonas aeruginosa pneumonia. Clin Diagn Lab Immunol 5:882-887.

12.
Song, Z. J., H. K. Johansen, V. Faber, and N. Høiby. 1997. Ginseng treatment enhances bacterial clearance and decreases lung pathology in athymic rats with chronic P. aeruginosa pneumonia. Acta Pathol. Microbiol. Scand. 105:438-444.

13.
Yang, G. Z., T. Bao, and Y. L. Yu. 1987. Immune modulating effects of ginseng in vivo and in vitro. Communication of Medical Research (in Chinese) 16:220-221.

Students and Postdoctoral fellows involved:

Post-doc	1. Dr. Zhijun Song
Graduate Students	2. Mr. Kok-Fai Kong