TABLE 1.
Strain | Isolate | MIC (mg/liter TMP-SMX) | Mutation(s) |
Descriptionb | ||||||
---|---|---|---|---|---|---|---|---|---|---|
DHFR/FolA | DHPS/FolP | FolP2 | FolE | FtsH | GpgS | ThyA | ||||
ATCC 33727 | 2-4 | >32-608 | Ile99Thr | Ser27Pro | 1-bp deletion at position −64 position | SNP at position −37, transcriptional regulator, TetR family; V560G sensory box/GGDEF family protein; d-alanyl–d-alanine carboxypeptidase/integral membrane efflux protein (position −88/−33); SNP at position +60, CAIB/BAIF family; 2-bp →CA (R209Q) at position 625, enoyl-CoA hydratase; 9 others | ||||
MDA0897 | 1-5 | >32-608 | Met30Arg | SNP at position −16 | Siderophore biosynthesis nonribosomal peptide synthetase modules at bacillibactin synthetase component F (I10849L); 13 others | |||||
MDA5529 | 2-5 | >32-608 | Phe26Ser | Gly210Glu | SNP at positions −65 and −12, GntR family; W31* sensor histidine kinase MtrB; R142M, enoyl-CoA hydratase; 5 others | |||||
MDA3349 (c) | 1-4 | 16-304 | Phe36Leu | Val101Ala | C6→7 (gene fusion) | 2 others | ||||
MDA0897 | 2-1 | 16-304 | Ile99Leu | Phe26Cys | Lys212Glu | N98K, methionine ABC transporter; 5 others | ||||
MDA0897 | 2-3 | 16-304 | Ile99Leu | Phe26Cys | Lys212Glu | P99L and N98K, methionine ABC transporter; 3 others | ||||
ATCC 33727 | 1-4 | 16-304 | Ile155Thr | Phe26Cys | Insertion at nucleotide 227 | Δ12-bp sensory box/GGDEF protein; 2-bp →CA (R209Q) at position 625, enoyl-CoA hydratase; 5 others | ||||
ATCC 10905 | 1-1 | 16-304 | Ile155Thr | Phe26Cys | Thr116Pro | SNP at position −150 | S269L, sensor histidine kinase MtrB; K53E transcriptional regulator, TetR family; S183A, PstB; 7 others | |||
ATCC 10905 | 1-2 | 16-304 | Ile155Thr | Phe26Cys | Thr116Pro | SNP at position −150 | S269L, sensor histidine kinase MtrB; 5 others | |||
MDA3349 (c) | 1-33 | 16-304 | Phe36Leu | C6→7 (gene fusion) | Transcriptional regulator, MarR family, E90*; siderophore biosynthesis nonribosomal peptide synthetase modules at bacillibactin synthetase component F (A6732V); 2 others | |||||
MDA3349 (c) | 1-38 | 16-304 | Phe36Leu | C6→7 (gene fusion) | Transcriptional regulator, MarR family, E90*; siderophore biosynthesis nonribosomal peptide synthetase modules at bacillibactin synthetase component F (A6732V); 2 others | |||||
MDA3732 (c) | 1-1 | 16-304 | Phe36Leu | C6→7 (gene fusion) | TC→CA at position −63 | P253T, transcriptional regulator, AraC family | ||||
ATCC 10905 | 2-1 | 16-304 | Phe26Cys | 2 others | ||||||
ATCC 10905 | 2-2 | 16-304 | Phe26Ser, Glu164Asp | 6 others | ||||||
MDA5529 | 1-4 | 16-304 | Phe26Leu | C6→5 | R142M, enoyl-CoA hydratase; 4 others | |||||
ATCC 33727 | 1-2 | 16-304 | Phe26Cys | Insertion at nucleotide 227 | Δ12-bp sensory box/GGDEF protein; 2-bp → CA (R209Q) at position 625, enoyl-CoA hydratase; 6 others | |||||
BAA2227 | 2-4 | 16-304 | Phe13Ser | Lys212Glu | SNP at position −27, transcriptional regulator, AraC family; 7 others | |||||
MDA3139 | 2-1 | 16-304 | Phe13Leu | C6→7 (gene fusion) | SNP at position −61, Glu215Gln | +G at nucleotide 12, integral membrane protein (rhomboid family); L371P, methionine ABC transporter; SNP at position −175, enoyl-CoA hydratase; 14 others | ||||
MDA3139 | 2-3 | 16-304 | Phe13Leu | C6→7 (gene fusion) | SNP at position −61, Glu215Gln | Siderophore biosynthesis nonribosomal peptide synthetase modules at bacillibactin synthetase component F (F1011S); L371P, methionine ABC transporter; 15 others | ||||
MDA3349 (c) | 1-31 | 16-304 | Phe13Ser, Asp172Glu | 12-bp deletion | Asp770Asp | SNP at position −34, integral membrane protein (rhomboid family); 1 other | ||||
MDA3397 | 2-3 | 16-304 | Phe13Cys | Arg243Cys | Δ144-bp transcription repair-coupling factor; *210E transcriptional regulator, TetR family; 7 others | |||||
MDA3397 | 2-5 | 16-304 | Phe13Cys | Arg243Cys | 4 others | |||||
MDA5529 | 2-1 | 16-304 | Phe26Ser | Gly210Glu | W31* sensor histidine kinase MtrB; R142M, enoyl-CoA hydratase; 6 others | |||||
BAA2227 | 1-1 | 16-304 | Ile112Thr | d-Alanyl–d-alanine carboxypeptidase/integral membrane efflux protein (position −80/−41); F458Y, CAIB-BAIF family; 15 others | ||||||
BAA2227 | 1-3 | 16-304 | Ile112Thr | Transcriptional regulator, MarR family, R136C; I36S, PstB; 13 others | ||||||
MDA3349 (c) | 2-18 | 16-304 | C6→7 (gene fusion) | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-69 | 16-304 | I131T, SNP at position −53 | 8 others | ||||||
MDA3139 | 1-1 | 8-152 | Ile155Thr | Phe13Ser | Lys212Glu | Transcriptional regulator, MarR family, at position −30; Δ1 bp at position 9, transcription repair-coupling factor; 12 others | ||||
MDA3139 | 1-5 | 8-152 | Ile155Thr | Phe13Ser | Lys212Glu | Asp473Gly | Transcriptional regulator, MarR family, at position −30; Δ1 bp at position 9, transcription repair-coupling factor; 12 others | |||
MDA0666 | 1-2 | 8-152 | Ile30Thr | Phe13Cys | C5→6 | P34A, transcriptional regulator, ArsR family; insertion at position 632 and L429P, sensory box/GGDEF family protein; 12 others | ||||
MDA0666 | 1-1 | 8-152 | Ile30Thr | Phe13Cys | SNP at position −135 | P34A, transcriptional regulator, ArsR family; insertion at position 632, sensory box/GGDEF family protein; 10 others | ||||
MDA3349 (c) | 1-7 | 8-152 | Phe36Leu | C6→7 (gene fusion) | 5 others | |||||
MDA3349 (c) | 1-1 | 8-152 | Phe36Leu | C6→7 (gene fusion) | 2 others | |||||
MDA3732 (c) | 1-2 | 8-152 | Phe36Leu | C6→7 (gene fusion) | TC→CA at position −63 | P253T, transcriptional regulator, AraC family | ||||
BAA2227 | 2-2 | 8-152 | Phe13Ser | Lys212Glu | SNP at position −27, transcriptional regulator, AraC family; 8 others | |||||
MDA5529 | 1-5 | 8-152 | Phe26Leu | C6→5 | *798Trp | R142M, enoyl-CoA hydratase; 3 others | ||||
MDA3349 (c) | 2-110 | 8-152 | Asp172Glu | Asp770Asp | SNP at positions −44 and −50, GntR family; 2 others | |||||
MDA3349 (c) | 2-16 | 8-152 | Asp172Glu | Asp770Asp | 3 others | |||||
MDA3349 (c) | 2-93 | 8-152 | Asp172Glu | Asp770Asp | 2 others | |||||
MDA3349 (c) | 2-12 | 8-152 | Asp172Glu | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-89 | 8-152 | Asp172Glu | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-94 | 8-152 | Asp172Glu | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-103 | 8-152 | Asp172Glu | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-3 | 8-152 | C6→5, Arg82Gln | |||||||
MDA3349 (c) | 2-13 | 8-152 | C6→7 (gene fusion) | Asp770Asp | 1 other | |||||
MDA3349 (c) | 2-106 | 8-152 | C6→7 (gene fusion) | Asp770Asp | 2 others | |||||
MDA3732 (c) | 2-1 | 8-152 | Asp770Asp | P253T, transcriptional regulator, AraC family; 2 others | ||||||
MDA3732 (c) | 2-2 | 8-152 | Asp770Asp | SNP at position −39, integral membrane protein (rhomboid family); P253T, transcriptional regulator, AraC family; 3 others | ||||||
MDA3349 (c) | 1-47 | 8-152 | Δ2-bp transcription repair-coupling factor | |||||||
MDA3349 (c) | 1-48 | 4-76 | C6→7 (gene fusion) | 4 others | ||||||
MDA3349 (c) | 1-14 | 4-76 | Arg262His | 1 other | ||||||
MDA3349 (c) | 2-42 | 4-76 | Arg82Gln | Transcriptional regulator, MarR family, E73*; SNP at position −60, transcriptional regulator, ArsR family; T170P, transcriptional regulator, TetR family; 2 others | ||||||
MDA3349 (c) | 1-19 | 4-76 | 12-bp deletion | Asp770Asp | SNP at position −34, integral membrane protein (rhomboid family); R454C, sensor histidine kinase MtrB; 2 others | |||||
MDA3349 (c) | 2-65 | 1-19 | E84K, transcription repair-coupling factor | |||||||
MDA3349 (c) | 2-66 | 1-19 | 4 others | |||||||
MDA3349 (c) | 1-26 | 1-19 | 1 other | |||||||
MDA3349 (c) | 1-44 | 1-19 | 1 other | |||||||
MDA3349 (c) | 1-11 | 1-19 | 1 other |
Isolates are arranged in decreasing order of TMP-SMX MICs. MDA3349 isolates 1-47, 1-15, 1-43, 2-41, and 2-6 had MICs of 1-19 mg/liter TMP-SMX and had no mutations. Abbreviations: DHFR/FolA, dihydrofolate reductase; DHPS/FolP, dihydropteroate synthase; FolP2, dihydropteroate synthase homolog; FolE, GTP cyclohydrolase I; FtsH, cell division protein; GpgS, glucosyl-3-phosphoglycerate synthase; ThyA, thymidylate synthase; SNP, single nucleotide polymorphism. (c) represents Nocardia cyriacigeorgica strains. All other strains are Nocardia nova strains.
Mutations listed in this column are those that occur in genes not directly involved in the folate biosynthesis pathway but are seen in more than 1 strain, suggesting that they may be adaptive. If a gene is affected within multiple isolates of the same strain, it is listed as “other.” See Data Sets S1 and S2 in the supplemental material for complete details of all mutations observed in these isolates.