TABLE 4.
Amino acid changes resulting from mutations in gyrA and grlA eQRDR coding sequence and the associated MICs of NXL101 and various fluoroquinolones against various S. aureus strains before and after selection for NXL101 resistance
WT or mutant straina | MIC (mg liter−1)b
|
Mutation in QRDR
|
|||||||
---|---|---|---|---|---|---|---|---|---|
Fluoroquinolone resistance (WT strains)
|
NXL101 resistance (GyrA [mutant strains])c | ||||||||
NXL101 | NOR | CIP | LVX | SPX | MFX | GyrA | GrlA | ||
Mu50 | |||||||||
WT | 0.25 | 128 | 32 | 16 | 32 | 8 | S84L | S80F | |
Mutant | 64 | 128 | 32 | 32 | 64 | 16 | D83N | ||
N315 | |||||||||
WT | 0.25 | 8 | 2 | 0.5 | 0.125 | 0.125 | |||
Mutant | 2 | 2 | 0.5 | 0.25 | 0.125 | 0.125 | —d | ||
MRSA252 | |||||||||
WT | 0.125 | 128 | 128 | 16 | 16 | 4 | S84L | S80F | |
Mutant | 2 | 128 | 128 | 16 | 8 | 4 | V45A | ||
MSSA476 | |||||||||
WT | 0.5 | 2 | 1 | 0.5 | 0.125 | 0.125 | |||
Mutant | 64 | 1 | 0.5 | 0.25 | 0.125 | 0.125 | D83N | ||
NCTC8325 | |||||||||
WT | 0.25 | 0.5 | 0.5 | 0.25 | 0.25 | 0.25 | |||
Mutant | 64 | 0.25 | 0.25 | 0.125 | 0.125 | 0.125 | M121K | ||
COL | |||||||||
WT | 0.25 | 2 | 0.5 | 0.5 | 0.25 | 0.125 | |||
Mutant | 32 | 1 | 0.5 | 0.25 | 0.25 | 0.25 | D83N | ||
MW2 | |||||||||
WT | 0.25 | 2 | 1 | 0.25 | 0.125 | 0.125 | |||
Mutant | 64 | 1 | 1 | 0.25 | 0.125 | 0.125 | M121K | ||
Bontemps | |||||||||
WT | 2 | 32 | 4 | 1 | 0.25 | 0.25 | S80F | ||
Mutant | 32 | 32 | 4 | 2 | 0.5 | 1 | D83G S84T R92C | ||
1 | |||||||||
WT | 0.25 | 32 | 16 | 1 | 0.5 | 0.25 | I45M S80F | ||
Mutant | 16 | 32 | 8 | 2 | 0.5 | 0.5 | D83G | ||
2 | |||||||||
WT | 0.5 | 4 | 1 | 0.5 | 0.25 | 0.125 | |||
Mutant | 64 | 4 | 1 | 0.5 | 0.25 | 0.25 | D83N | ||
3 | |||||||||
WT | 0.125 | 2 | 0.5 | 0.25 | 0.125 | 0.125 | |||
Mutant | 64 | 2 | 1 | 0.25 | 0.25 | 0.125 | D83N | ||
4 | |||||||||
WT | 0.125 | 128 | 64 | 32 | 32 | 8 | S84V | S80F | |
Mutant | 32 | 128 | 128 | 128 | 128 | 16 | D83N | ||
5 | |||||||||
WT | 0.125 | 2 | 0.5 | 0.25 | 0.125 | 0.125 | |||
Mutant | 64 | 1 | 1 | 0.125 | 0.125 | 0.125 | D83N | ||
6 | |||||||||
WT | 0.25 | 2 | 0.5 | 0.25 | 0.125 | 0.125 | |||
Mutant | 32 | 1 | 0.5 | 0.125 | 0.125 | 0.125 | D83N | ||
7 | |||||||||
WT | 0.25 | 64 | 16 | 8 | 16 | 2 | S84L | S80Y | |
Mutant | 32 | 16 | 16 | 2 | 4 | 2 | D83N | ||
8 | |||||||||
WT | 0.25 | 128 | 32 | 16 | 32 | 4 | M18I S84 L | S80Y | |
Mutant | 16 | 32 | 32 | 4 | 8 | 2 | D83N | ||
9 | |||||||||
WT | 0.25 | 64 | 32 | 8 | 8 | 2 | S84L | S80Y | |
Mutant | 32 | 32 | 32 | 4 | 4 | 2 | D83N | ||
10 | |||||||||
WT | 0.125 | 128 | 128 | 32 | 32 | 4 | S84V | S80F | |
Mutant | 16 | 128 | 128 | 16 | 16 | 8 | D83N | ||
11 | |||||||||
WT | 0.25 | 2 | 1 | 0.5 | 0.25 | 0.125 | |||
Mutant | 16 | 2 | 2 | 1 | 1 | 1 | D83N | ||
12 | |||||||||
WT | 0.125 | 2 | 0.5 | 0.25 | 0.125 | 0.125 | |||
Mutant | 16 | 1 | 1 | 0.125 | 0.125 | 0.125 | D83G | ||
13 | |||||||||
WT | 0.125 | 16 | 8 | 1 | 1 | 0.5 | I45M S80F | ||
Mutant | 16 | 16 | 16 | 1 | 1 | 1 | D83N | ||
14 | |||||||||
WT | 0.125 | 128 | 128 | 32 | 32 | 16 | S84V | S80F | |
Mutant | 16 | 128 | 128 | 16 | 16 | 16 | D83N | ||
15 | |||||||||
WT | 0.5 | 1 | 0.25 | 0.25 | 0.125 | 0.125 | |||
Mutant | 16 | 0.5 | 0.13 | 0.125 | 0.125 | 0.125 | A94P | ||
16 | |||||||||
WT | 0.25 | 2 | 0.5 | 0.5 | 0.125 | 0.125 | |||
Mutant | 64 | 2 | 0.5 | 0.5 | 0.25 | 0.125 | D83N |
Mutant strains were isolated by selection on plates containing NXL101.
NOR, norfloxacin; CIP, ciprofloxacin; LVX, levofloxacin; SPX, sparfloxacin; MFX, moxifloxacin.
There were no NXL101 resistance GrlA mutations.
-, a mutation of Asp437 to Val was seen in the GyrB subunit of the NXL101-resistant variant of S. aureus N315.