Table 2.
Antibacterial efficacies of inhibitors that function through the RNAP switch region
| Organism | Minimum Inhibitory Concentration (µg/ml)a-f |
|||
|---|---|---|---|---|
| Myx | Cor | Rip | Lpm | |
| Gram-positive bacteria | ||||
| Staphylococcus aureus ATCC12600 MSSA | 1.0 | 4.9 | 13 | 3.5 |
| Staphylococcus aureus BAA-1707 MRSA (MW2) | 1.3 | 4.9 | 13 | 4.0 |
| Staphylococcus aureus BAA-1717 MRSA (USA300) | 1.3 | 4.9 | 16g | 3.2 |
| Staphylococcus aureus ATCC12600-Rif RRSA (βH516V) | 1.0 | 8.0 | 13 | 4.5 |
| Staphylococcus aureus ATCC12600-Rif RRSA (βH526N) | 1.0 | 10 | 13 | 4.5 |
| Staphylococcus aureus ATCC12600-Rif RRSA (βH526Y) | 1.0 | 8.0 | 13 | 2.8 |
| Staphylococcus aureus ATCC12600-Rif RRSA (βS531L) | 1.0 | 8.0 | 13 | 2.3 |
| Enterococcus faecalis ATCC19433 | 7.8 | >40 | >40 | 7.4 |
| Enterococcus faecium ATCC19434 | 1.1 | 7.1 | 13 | 2.1 |
| Streptococcus pneumoniae ATCC49619 | 2.9 | 5.5 | >40 | 4.1 |
| Clostridium difficile ATCC9689 | 3.1 | 0.78 | 3.1 | 0.012 |
| Mycobacterium tuberculosis H37Rv | 1.6 | 3.1 | >40 | 3.1 |
| Bacillus anthracis Vollum-1B | 13 | 13 | >40 | 0.78 |
| Gram-negative bacteria | ||||
| Escherichia coli DH5α | >40 | >40 | >40 | >40 |
| Escherichia coli D21f2tolC (rfa tolC) | 0.4 | 0.8 | 1.1 | 2 |
| Haemophilus influenzae ATCC33391 | 16 | >40 | >40 | >40 |
| Moraxella catarrhalis ATCC25238 | 6.1 | 12 | 13 | 11 |
| Francisella tularensis SCHU4 | 13 | >40 | >40 | 25 |
Compounds were Myx B (synthesized as in [27]; provided by Y.W.E.), Cor A (isolated as in [37]; provided by R.J. and H.I.), Rip A (isolated as in [41]; provided by R.J. and H.I.), and Lpm A3 (isolated as in [48]; provided by S.D.).
Data for S. aureus. E. faecalis., E. faecium., and E. coli are from spiral gradient endpoint assays performed essentially as in [74–76] (A.S., D.D., and R.H.E., unpublished data). Assays employed exponential-gradient plates containing 150 mm × 4 mm Mueller-Hinton II cation-adjusted agar (BD, Inc.) and 0.1–40 µg/ml of test compound. Plates were prepared using an Autoplate 4000 spiral plater (Spiral Biotech, Inc.). Saturated overnight cultures were swabbed radially onto plates, and plates were incubated for 16 h at 37°C. For each culture, the streak length was measured using a clear plastic template (Spiral Biotech, Inc.), the test-compound concentration at the streak endpoint was calculated using the program SGE (Spiral Biotech, Inc.), and the MIC was defined as the calculated test-compound concentration at the streak endpoint.
Data for S. pneumoniae, H. influenzae, and M. catarrhalis are from spiral gradient endpoint assays, performed as above, except that plates contained GC II agar (Teknova, Inc.)and were incubated in a 5% CO2/95% air atmosphere in an Anoxomat Mark II (Mart Microbiology, Inc.) (A.S. and R.H.E., unpublished data).
Data for C. difficile are from anaerobic broth microdilution assays [77] (A.S. and R.H.E., unpublished data).
Data for M. tuberculosis are from microplate Alamar Blue assays [78] (M.T., N.C., and R.H.E., unpublished data).
Data for B. anthracis and F. tularensis are from aerobic broth microdilution assays [79] (M.T., N.C., and R.H.E., unpublished data).
MIC50.