Abstract
Aspergillus fumigatus mutants resistant to amphotericin B were selected in the laboratory following UV irradiation. A total of 18 colonies (frequency 1.8 x 10-7) that grew in the presence of amphotericin B (8 mg/L and 16 mg/L) on peptone yeast extract glucose agar were tested for their susceptibility to amphotericin B, nystatin, azoles, and the echinocandin L-743872. Ten of the 18 isolates showed an eight-fold rise in amphotericin B MIC (4 mg/L) compared with the susceptible parent whereas the remaining isolates showed a 16 to 32-fold rise in amphotericin B MIC (8-16 mg/L). Subculturing of three representatives from each of the groups that had MIC values of 4 mg/L and 8-16 mg/L for six cycles revealed that the resistance trait was stably expressed. All amphotericin B-resistant isolates showed a significant level of cross-resistance to nystatin but not to azoles and L-743872. Kill-curve studies with amphotericin B revealed that the killing of the resistant isolates was significantly less than that of the susceptible parent strain. These results show that amphotericin B-resistant mutants of A. fumigatus can be isolated in the laboratory following a single-step UV-induced mutagenesis and suggest that similar mechanisms could operate in nature for the emergence of resistance in clinical isolates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 615-619 |
| Number of pages | 5 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 41 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 1998 |
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ASJC Scopus subject areas
- Pharmacology
- Microbiology
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In-vitro isolation and antifungal susceptibility of amphotericin B-resistant mutants of Aspergillus fumigatus. / Manavathu, Elias Kurian; Alangaden, George J.; Chandrasekar, Pranatharthi H.
In: Journal of Antimicrobial Chemotherapy, Vol. 41, No. 6, 01.06.1998, p. 615-619.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In-vitro isolation and antifungal susceptibility of amphotericin B-resistant mutants of Aspergillus fumigatus
AU - Manavathu, Elias Kurian
AU - Alangaden, George J.
AU - Chandrasekar, Pranatharthi H.
PY - 1998/6/1
Y1 - 1998/6/1
N2 - Aspergillus fumigatus mutants resistant to amphotericin B were selected in the laboratory following UV irradiation. A total of 18 colonies (frequency 1.8 x 10-7) that grew in the presence of amphotericin B (8 mg/L and 16 mg/L) on peptone yeast extract glucose agar were tested for their susceptibility to amphotericin B, nystatin, azoles, and the echinocandin L-743872. Ten of the 18 isolates showed an eight-fold rise in amphotericin B MIC (4 mg/L) compared with the susceptible parent whereas the remaining isolates showed a 16 to 32-fold rise in amphotericin B MIC (8-16 mg/L). Subculturing of three representatives from each of the groups that had MIC values of 4 mg/L and 8-16 mg/L for six cycles revealed that the resistance trait was stably expressed. All amphotericin B-resistant isolates showed a significant level of cross-resistance to nystatin but not to azoles and L-743872. Kill-curve studies with amphotericin B revealed that the killing of the resistant isolates was significantly less than that of the susceptible parent strain. These results show that amphotericin B-resistant mutants of A. fumigatus can be isolated in the laboratory following a single-step UV-induced mutagenesis and suggest that similar mechanisms could operate in nature for the emergence of resistance in clinical isolates.
AB - Aspergillus fumigatus mutants resistant to amphotericin B were selected in the laboratory following UV irradiation. A total of 18 colonies (frequency 1.8 x 10-7) that grew in the presence of amphotericin B (8 mg/L and 16 mg/L) on peptone yeast extract glucose agar were tested for their susceptibility to amphotericin B, nystatin, azoles, and the echinocandin L-743872. Ten of the 18 isolates showed an eight-fold rise in amphotericin B MIC (4 mg/L) compared with the susceptible parent whereas the remaining isolates showed a 16 to 32-fold rise in amphotericin B MIC (8-16 mg/L). Subculturing of three representatives from each of the groups that had MIC values of 4 mg/L and 8-16 mg/L for six cycles revealed that the resistance trait was stably expressed. All amphotericin B-resistant isolates showed a significant level of cross-resistance to nystatin but not to azoles and L-743872. Kill-curve studies with amphotericin B revealed that the killing of the resistant isolates was significantly less than that of the susceptible parent strain. These results show that amphotericin B-resistant mutants of A. fumigatus can be isolated in the laboratory following a single-step UV-induced mutagenesis and suggest that similar mechanisms could operate in nature for the emergence of resistance in clinical isolates.
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U2 - 10.1093/jac/41.6.615
DO - 10.1093/jac/41.6.615
M3 - Article
VL - 41
SP - 615
EP - 619
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 6
ER -