Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296

Avital Mazar Ben-Josef, Elias K. Manavathu, David Platt, Jack D. Sobel

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume44
Issue number2
DOIs
StatePublished - Aug 26 1999

Fingerprint

Cell Wall
Calcium
Candida albicans
Cell Aggregation
Antifungal Agents
CAN 296
Candida glabrata
Mucor
Azoles
Barium
Manganese
Cobalt
Lithium
Magnesium
Cations
Copper
Dialysis
Potassium
Fungi
Hot Temperature

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296. / Ben-Josef, Avital Mazar; Manavathu, Elias K.; Platt, David; Sobel, Jack D.

In: Journal of Antimicrobial Chemotherapy, Vol. 44, No. 2, 26.08.1999, p. 217-222.

Research output: Contribution to journalArticle

Ben-Josef, Avital Mazar ; Manavathu, Elias K. ; Platt, David ; Sobel, Jack D. / Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296. In: Journal of Antimicrobial Chemotherapy. 1999 ; Vol. 44, No. 2. pp. 217-222.
@article{5ed5d015c7fd46fb83e84c42f2713212,
title = "Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296",
abstract = "CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.",
author = "Ben-Josef, {Avital Mazar} and Manavathu, {Elias K.} and David Platt and Sobel, {Jack D.}",
year = "1999",
month = "8",
day = "26",
doi = "10.1093/jac/44.2.217",
language = "English (US)",
volume = "44",
pages = "217--222",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Involvement of calcium inhibitable binding to the cell wall in the fungicidal activity of CAN-296

AU - Ben-Josef, Avital Mazar

AU - Manavathu, Elias K.

AU - Platt, David

AU - Sobel, Jack D.

PY - 1999/8/26

Y1 - 1999/8/26

N2 - CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.

AB - CAN-296 is a heat stable, complex carbohydrate (molecular mass 4300 Da) isolated from the cell wall of the filamentous fungus Mucor rouxii. It possesses potent in-vitro fungicidal activity against a wide spectrum of pathogenic yeasts, including azole-resistant isolates of Candida albicans and Candida glabrata. As a preliminary step in the study of the mode of action of this novel antifungal agent, we investigated the effect of various cations on the antifungal activity as well as the binding of CAN-296 to intact cells and cell-wall fractions of C. albicans. The antifungal activity of CAN-296 was inhibited by low concentrations of calcium, magnesium and lithium and by high concentrations of barium, cobalt and manganese, but not by potassium and copper. The calcium-mediated inhibition of the antifungal activity of CAN-296 was readily reversible by the removal of calcium by dialysis, and the fungicidal activity of the inhibited compound was fully restored. The uptake/binding of CAN-296 to intact cells and to the cell-wall fraction of C. albicans was time and concentration dependent. Maximum uptake/binding was obtained at 5 mg/L within 60 min and was associated with the aggregation of intact cells. Washing intact cells and the cell-wall fraction preincubated with radiolabelled CAN-296 with 150-fold excess of unlabelled compound failed to remove CAN-296 associated with the intact cells and the cell-wall fraction, suggesting that the binding of CAN-296 to C. albicans is tight. The uptake/binding of CAN-296 and the drug-mediated aggregation of intact cells were inhibited by calcium in a concentration-dependent manner. The fact that CAN-296 is a fungicidal agent that binds to intact cells and the cell-wall fraction of C. albicans very tightly, together with the observation that calcium was able to inhibit the fungicidal activity as well as the uptake/binding of CAN-296, suggests that the mode of action of this novel antifungal agent may involve interaction with the cell wall of C. albicans.

UR - http://www.scopus.com/inward/record.url?scp=0032766451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032766451&partnerID=8YFLogxK

U2 - 10.1093/jac/44.2.217

DO - 10.1093/jac/44.2.217

M3 - Article

C2 - 10473228

AN - SCOPUS:0032766451

VL - 44

SP - 217

EP - 222

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 2

ER -