Therapeutic evaluation of polyamine analogue drug candidates against Enterocytozoon bieneusi in a SCID mouse model

Xiaochuan Feng, Venudhar K. Reddy, Harriet Mayanja-Kizza, Louis M. Weiss, Laurence J. Marton, Saul Tzipori

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Enterocytozoon bieneusi is the most common cause of chronic diarrhea in individuals with human immunodeficiency virus infection or AIDS, and there is no effective therapy. The inhibitory activities of polyamine analogues (PG-11157, PG-11158, and PG-11302) against E. bieneusi infection were evaluated in SCID mice preconditioned with anti-gamma interferon monoclonal antibody intraperitoneally (i.p.). Mice were challenged orally with 104 E. bieneusi spores, and groups of mice were treated orally or i.p. 14 days later for 7 days. The inhibitory activities of the drugs against infection were determined by enumerating the E. bieneusi spores in feces three times a week by an immunofluorescence assay. Immunohistochemistry staining confirmed the infection within enterocytes. Oral administration of the analogues PG-11157 (at 150 or 75 mg/kg of body weight/day) and PG-11302 (at 250 mg/kg/day) had significant inhibitory activity (96.2 to 99.6%) that was slightly better than that of fumagillin (1 mg/kg/day; 93.7%). The inhibitory activity with i.p. injection was significant only with PG-11302 at 20 mg/kg/day. While the treatments considerably reduced the levels of spore excretion, neither polyamine analogues nor fumagillin was able to completely eliminate E. bieneusi, as excretion reappeared within 7 days after the end of treatment. Drug toxicity was apparent during treatment, but it disappeared at the end of treatment. These results warrant further examination of the analogues PG-11157 and PG-11302.

Original languageEnglish (US)
Pages (from-to)2417-2423
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Enterocytozoon
SCID Mice
Polyamines
Synthetic Prostaglandins
Spores
Pharmaceutical Preparations
Infection
Therapeutics
Enterocytes
Virus Diseases
Drug-Related Side Effects and Adverse Reactions
Feces
Interferon-gamma
Fluorescent Antibody Technique
Oral Administration
Diarrhea
Acquired Immunodeficiency Syndrome
Immunohistochemistry
Monoclonal Antibodies
Body Weight

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Therapeutic evaluation of polyamine analogue drug candidates against Enterocytozoon bieneusi in a SCID mouse model. / Feng, Xiaochuan; Reddy, Venudhar K.; Mayanja-Kizza, Harriet; Weiss, Louis M.; Marton, Laurence J.; Tzipori, Saul.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 6, 06.2009, p. 2417-2423.

Research output: Contribution to journalArticle

Feng, Xiaochuan ; Reddy, Venudhar K. ; Mayanja-Kizza, Harriet ; Weiss, Louis M. ; Marton, Laurence J. ; Tzipori, Saul. / Therapeutic evaluation of polyamine analogue drug candidates against Enterocytozoon bieneusi in a SCID mouse model. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 6. pp. 2417-2423.
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