TABLE 1.
Effect of vancomycin exposure on cytoplasmic PG intermediates in VSEfm and VREfm and comparison with MRSA (28)
| Concn (time zero concn) forb: |
|||||||
|---|---|---|---|---|---|---|---|
| VSEfm |
VREfm |
MRSA |
|||||
| Intermediatea | −Vm | +Vm (1.5 h) | −Vm | +Vm (1.5 h) | +Vm (18 h) | −Vm | +Vm (1.5 h) |
| UDP-linked intermediates (μM) | |||||||
| UDP-NAG | 940 (20) | 290 (20) | 590 (40) | 510 (30) | 470 (30) | 740 (60) | 77 (10) |
| UDP-NAM | 1,130 (60) | 740 (50) | 480 (20) | 740 (20) | 320 (30) | 1,250 (60) | 5,200 (900) |
| UDP-Mono | 113 (2) | 7.2 (0.5) | 80 (10) | 63 (4) | 35 (1) | 81 (7) | 2,900 (500) |
| UDP-Di | 55 (6) | 4.3 (1.5) | 95 (8) | 24 (2) | 47.8 (0.4) | 32 (6) | 110 (50) |
| UDP-Tri | 30 (5) | 97 (7) | 48 (7) | 43 (1) | 26 (4) | 10 (2) | 35 (8) |
| UDP-Penta | 590 (20) | 2,280 (120) | 356 (8) | 900 (40) | 190 (90) | 260 (30) | 62,000 (2,000) |
| UDP-Pentadepsi | ND | ND | 13.4 (0.4) | 730 (10) | 290 (50) | ND | ND |
| UDP-Tetra | ND | ND | 15.6 (0.4) | 774 (6) | 44 (5) | ND | ND |
| UDP-Penta-d-iAsp | ND | ND | ND | ND | 1.3 (0.2) | ND | ND |
| UDP-Pentadepsi-d-iAsp | ND | ND | 13.2 (0.9) | 46 (2) | 27 (2) | ND | ND |
| UDP-Tetra-d-iAsp | ND | ND | ND | ND | 2.1 (0.1) | ND | ND |
| UDP-Sum | 2,860 (60) | 3,500 (200) | 1,470 (130) | 3,820 (30) | 1,460 (60) | 2,380 (90) | 71,000 (1,900) |
| Amino acid and d-Ala–d-Ala intermediates (mM) | |||||||
| l-Ala | 52 (8) | 17.4 (0.6) | 29 (2) | 20.1 (0.8) | 15.2 (0.9) | 67 (7) | 64 (7) |
| d-Ala | 26 (3) | 5.2 (0.2) | 22 (2) | 12 (3) | 11 (1) | 48 (8) | 46 (16) |
| d-Ala–d-Ala | 2.8 (0.4) | 0.3 (0.1) | 0.71 (0.05) | 0.4 (0.1) | 0.12 (0.07) | 0.9 (0.3) | 17 (2) |
| d-Ala–d-Lac | ND | ND | 0.11 (0.01) | 2.8 (0.1) | 2.1 (0.3) | ND | ND |
| l-Glu | 126 (9) | 24.2 (0.6) | 81 (3) | 95 (2) | 57 (9) | 250 (30) | 210 (30) |
| d-Glu | 10.7 (0.2) | 4.7 (0.7) | 17.6 (0.3) | 51 (9) | 49 (2) | 200 (40) | 230 (50) |
| l-Lys | 11.1 (1.2) | 4.1 (0.4) | 11.8 (0.5) | 21 (1) | 12.6 (0.6) | 64 (5) | 79 (3) |
| l-Asp | 38 (4) | 9.3 (0.2) | 18.3 (0.4) | 21 (2) | 22 (3) | 96 (11) | 15 (8) |
| d-Asp | 22 (3) | 5 (1) | 14 (1) | 25.1 (0.5) | 15.7 (0.2) | 63 (9) | 15 (4) |
a
UDP-Mono, UDP-NAM–l-Ala; UDP-Di, UDP-NAM–l-Ala–d-Glu.
b
Values are mean ± SE (n = 3), Vm, vancomycin. UDP-NAG-enolpyruvate levels were not detectable (<0.5 μM). ND, not detectable.