TABLE 1.
Cu treatment leads to a misregulation of metal homeostasisa
| Gene | MGAS5005 gene product annotation | Log2FC(+Cu/–Cu) | P adj |
|---|---|---|---|
| CopY regulated | |||
| copZ | Copper chaperone | 4.41 | 0.0000 |
| copA | Copper-exporting ATPase | 4.39 | 0.0000 |
| copY | CopAB ATPase metal-fist type repressor | 4.49 | 0.0000 |
| CadC regulated | |||
| cadD | Cadmium resistance protein | 3.15 | 0.0000 |
| cadC | Cadmium efflux system accessory protein | 4.00 | 0.0000 |
| AdcR regulated | |||
| phtY | Internalin protein | −1.80 | 0.0000 |
| rpsN | 30S ribosomal protein S14 | −1.72 | 0.0000 |
| phtD | Histidine triad protein | −2.51 | 0.0000 |
| adcAII | Laminin-binding protein | −2.37 | 0.0000 |
| adhE | Acetaldehyde-CoA/alcohol dehydrogenase | −3.32 | 0.0000 |
| MtsR regulated | |||
| fhuG | Ferrichrome transporter permease | −1.99 | 0.0000 |
| fhuB | Ferrichrome transporter permease | −1.81 | 0.0000 |
| fhuD | Ferrichrome-binding protein | −1.91 | 0.0000 |
| fhuA | Ferrichrome ABC transporter ATP-binding protein | −1.75 | 0.0000 |
| nrdI.2 | Ribonucleotide reductase stimulatory protein | −1.57 | 0.0006 |
| nrdE.2 | Ribonucleotide-diphosphate reductase subunit alpha | −1.64 | 0.0001 |
| hupY | Cell surface protein | −2.29 | 0.0000 |
| hupZ | Hypothetical protein M5005_Spy_0652 | −2.25 | 0.0000 |
| siaD | ABC transporter ATP-binding protein | −2.34 | 0.0000 |
| siaC | Ferrichrome ABC transporter ATP-binding protein | −2.71 | 0.0000 |
| siaB | Ferrichrome transporter permease | −2.63 | 0.0000 |
| siaA | Ferrichrome-binding protein | −2.28 | 0.0000 |
| shp | Heme-binding protein | −1.80 | 0.0000 |
| shr | Fe3+-siderophore transporter | −1.94 | 0.0000 |
| GczA regulated | |||
| gczA | TetR family transcriptional regulator | 0.03 | 0.9378 |
| czcD | Cobalt-zinc-cadmium resistance protein | 0.46 | 0.2807 |
| GSH import | |||
| gshT | Amino acid ABC transporter substrate-binding protein | 0.90 | 0.1098 |
| tcyB | Amino acid ABC transporter permease | 0.83 | 0.0409 |
| tcyC | ABC transporter substrate-binding protein | 0.87 | 0.0443 |
GAS ΔcopA mutant strain was cultured with or without 5 μM added Cu for t = 5 h (n = 3). Total RNA was extracted, rRNA was depleted, and cDNA was generated and finally sequenced by Illumina. Differential gene expression was determined using DeSeq2 and is presented as the fold change (FC) in gene expression in the Cu-treated cultures relative to that in the untreated control. Only genes of interest are listed. These are genes regulated by metal-sensing transcriptional regulators CopY, CadC (45), AdcR (43), MtsR (44), and GczA (46), as well as those that encode components of the putative GSH uptake system (50). A complete list of differentially regulated genes is provided in Data Set S1.