Table 2.
Descriptions of the point mutations in Table 1 found in JH1-JH6
| No.* | Isolate in which mutation appears first | Mutated locus† | Locus previously implicated in resistance to | Description of mutated locus | Mutation‡ |
|---|---|---|---|---|---|
| 1 | JH1 | SAP011 (blaR1) (on the plasmid) | β-lactams (21) | Involved in regulation of β-lactamase gene blaZ and broad spectrum β-lactam resistance gene mecA | Deletion in A× 8 frameshifted last 70% of gene. |
| 2 | JH2 | SA1702 | Vancomycin and β-lactams (23, 39, 46, 47) | In operon with gene vraR, which is possibly involved in the regulation of cell wall synthesis | Amino acid change H164R |
| 3 | JH2 | SA0500 (rpoB) | Rifampin (18) | Codes for β-subunit of RNA polymerase | Amino acid change D471Y |
| 4 | Amino acid change A473S | ||||
| 5 | Amino acid change A477S | ||||
| 6 | Amino acid change E478D | ||||
| 7 | JH2 | SA0501 (rpoC) | Daptomycin (38) | Codes for β'-subunit of RNA polymerase | Amino acid change E854K |
| 8 | JH2 | SA1129 | Contains match to RNA binding motif | Amino acid change D296Y | |
| 9 | JH5 | SA1249 | Putative gene possibly in an operon with the gene murG, which is involved in cell wall synthesis | Deletion in G×9 frameshifted last 80% of gene. | |
| 10 | JH6 | SA1843 (agrC) | Vancomycin (24, 25) | Part of agr locus involved in qorum sensing and regulation of the expression of virulence and cell surface proteins | Deletion in T×9 frameshifted last 70% of gene. |
| 11 | JH6 | SA0019 (yycH) | Daptomycin (38) | In a gene cluster with the gene yycF and possibly involved in the regulation of the autolysin gene lytM | Substitution introduced stop codon, truncating protein to 10% of its length. |
| 12 | JH6 | Between divergently transcribed genes SAS014 and SA0411 (ndhF) | NdhF is the F-subunit of NADH dehydrogenase. | Deletion in T×7 upstream of both SAS014 and SA0411 | |
| 13 | JH6 | SA0582 | Similar to Na+/H+ antiporter subunit MrpE in B. subtilis | Synonymous substitution | |
| 14 | JH6 | SA0980 (isdE) | Involved in passage of heme-iron to cytoplasm during pathogenesis | Amino acid change A84V | |
| 15 | JH6 | SA1659 (prsA) | Chaperone that assists post-translocational folding of proteins at the cytoplasmic/cell wall interface | Deletion in A×7 frameshifted last 15% of gene. | |
| 16 | JH6 | SA2094 | Similar to malic/Na+-lactate antiporter MleN in B. subtilis | Amino acid change A94T | |
| 17 | JH6 | Between divergently transcribed genes SA2125 and SA2126 | SA2125 matches protein family consisting of arginases, agmatinases, and formiminoglutamases. | Substitution upstream of both SA2125 and SA2126 | |
| 18 | JH6 | SA2320 (pfoR) | Contains a match to a domain of a sugar specific permease | Synonymous substitution |
Because JH6 and JH9 have nearly identical MICs to the four antibiotics that were tested, the mutations 19–33 found only in JH9 are not described here. For descriptions of all the mutations, see SI Appendix, which gives the exact positions of the mutations in nucleotide coordinates and many references to relevant research articles.
*, Lists the numeric identifiers of the mutations used in Table 1.
†, The mutated locus is on the chromosome unless otherwise indicated. The SAXXXX and SAPXXX identifiers are the N315 identifiers for the genes (17). If a more descriptive identifier has been assigned to a gene, it is listed in parentheses.
‡, The nomenclature N × α is used to describe a run of identical bases: α is the number of bases in the run, and N is the repeated base.