Table 4.
Contribution to AZM resistance of mutations in genes pertaining to glutamine metabolism and other recurrent mutations
|
Strain |
AZM MIC (µg ml−1)* |
Mutations (AZM MIC µg ml−1)† |
|||||
|---|---|---|---|---|---|---|---|
|
spr0189 (L4) |
spr1120 (glnP)‡ |
spr1121 (glnQ)‡ |
spr0443 (glnR)‡ |
spr0538‡ |
spr1811‡ |
||
|
R6 |
0.25 |
|
|
|
|
|
|
|
M5§ |
1.0 |
G71R (0.5) |
N91S (1.0) |
|
|
||
|
M6§ |
1.0 |
G71R (0.5) |
|
G-75A|| (1.0) |
|
||
|
M14 |
1.0 |
G71R (0.5) |
CT-54C|| |
|
|
|
|
|
M15§ |
1.0 |
G71R (0.5) |
M651I (1.0) |
|
|
|
|
|
M16§ |
1.0 |
G71R (0.5) |
|
|
G-5C|| (1.0) |
||
|
M17§ |
1.0 |
G71R (0.5) |
|
|
|
Q134* (1.0) |
|
|
M18 |
1.0 |
Q67R (0.5) |
V179I (1.0) |
|
|
||
|
M19 |
0.5 |
G71R (0.5) |
H233D (1.0) |
|
|
||
|
M21 |
1.0 |
G71R (0.5) |
CT-54C|| |
|
|
|
|
|
M24 |
1.0 |
Q67R (0.5) |
A619D (1.0) |
|
|
|
|
|
M25 |
1.0 |
G71R (0.5) |
T46S (1.0) |
|
|
||
*The AZM MIC of the strain or mutant under aerobic atmosphere. All measurements were repeated a minimum of three times.
†Unless indicated otherwise, represent changes in amino acid and positions in the protein. An asterisk denotes a non-sense mutation. The AZM MIC indicated within parentheses are those of S. pneumoniae R6 transformed with the appropriate mutation.
‡Mutations in these genes were transformed into S. pneumoniae R6 harbouring G71R or Q67R mutations in ribosomal protein L4 (MIC AZM 0.5 µg ml−1). The AZM MICs indicated (within parenthesis) thus represent the sum of the contribution of the mutations along with the one in L4 mutations.
§The MICs of penicillin (0.0156 µg ml−1) and ceftriaxone (0.03 µg ml−1) for these transformants were equal to those of S. pneumoniae R6 wild-type or of S. pneumoniae R6 harbouring the G71R mutation in ribosomal protein L4.
||These represent intergenic mutations expressed in nucleotides. The position indicated corresponds to the nucleotide position upstream of the start codon.