Table 1. Validated genes in S. aureus impacting macrophage pathogenesis.
| Category | Gene name or JE2 Locus ID | Gene Function | Evidence for macrophage pathogenesis | Identification strategy | Validation Strategy | Invasion Effect | Survival effect |
|---|---|---|---|---|---|---|---|
| metabolism | arcR | arginine deiminase operon repressor | [68] | in vitro | Knockout | Increase | NS† |
| purR * | purine biosynthesis operon repressor | [69] | in vivo invasion | Knockout | Increase | NS | |
| purH | Bifunctional purine biosynthesis protein | [70] | in vivo invasion | Knockout | Increase | NS | |
| B7H15_07365 | hydrolase | This study | in vivo invasion | Knockout | Increase | NS | |
| kbl | glycine C-acetyltransferase | This study | in vivo invasion | Knockout | Increase | NS | |
| thiD | hydroxymethylpyrimidine/phosphomethylpyrimidine kinase | This study | in vivo invasion | Knockout | Increase | NS | |
| thyA | thymidylate synthase | [71] | in vivo invasion | CRISPRi | NS | Decrease | |
| cdr | CoA-disulfide reductase | This study | in vivo invasion | Knockout | Increase | Decrease | |
| pheT | Phenylalanine—tRNA ligase beta subunit | This study | in vivo invasion | CRISPRi | Increase | Decrease | |
| folB | Dihydroneopterin aldolase | This study | in vivo invasion | CRISPRi | Decrease | Decrease | |
| ansA | L-asparaginase, type II | This study | in vivo invasion | Knockout | Increase | NS | |
| ptaA | PTS glucose transporter subunit IIBC | This study | in vivo survival | Knockout | Increase | NS | |
| gntK | Gluconokinase | This study | in vivo invasion | Knockout | Increase | NS | |
| mnhD * | Na+/H+ antiporter subunit D | This study | in vivo invasion | Knockout | Increase | NS | |
| biofilm | nreC | Oxygen regulatory protein | [72] | in vitro | Knockout | Increase | NS |
| yycI * | regulatory protein | [73] | in vitro | Knockout | Increase | NS | |
| adherence and autolysis | atl * | bifunctional autolysin | [74] | in vivo invasion | Knockout | Increase | NS |
| fnbA * | fibronectin-binding protein A | [75,76] | in vivo survival | Knockout | Increase | NS | |
| clfA | clumping factor A | [77] | in vivo survival | Knockout | Increase | NS | |
| yycI * | regulatory protein | [78] | in vitro | Knockout | Increase | NS | |
| invasion | atl * | bifunctional autolysin | [79] | in vivo invasion | Knockout | Increase | NS |
| fnbA * | fibronectin-binding protein A | [75,76] | in vivo | Knockout | Increase | NS | |
| B7H15_05310 | putative Abi-domain protein | This study | in vitro | Knockout | Increase | NS | |
| iron metabolism | sirA | iron ABC transporter substrate-binding protein | [80] | in vivo invasion | Knockout | Increase | NS |
| virulence gene regulation | vraS | two-component sensor histidine kinase | [81] | in vitro | Knockout | Increase | NS |
| kdpD | sensor histidine kinase | [82] | in vivo invasion | Knockout | Increase | NS | |
| saeS | two-component sensor histidine kinase | [83–85] | in vivo invasion | Knockout | Increase | Decrease | |
| purR * | purine biosynthesis operon repressor | [69,86] | in vivo invasion | Knockout | Increase | NS | |
| yjbH * | transcriptional regulator | [87] | in vivo invasion and survival | Knockout | Increase | NS | |
| B7H15_06690 | transcriptional regulator | This study | in vivo invasion | CRISPRi | Decrease | Increase | |
| immune cell survival | clpX | protease | [89] | in vitro | CRISPRi | NS | Decrease |
| immune evasion | sdrE | MSCRAMM family adhesin | [88] | in vivo survival | Knockout | Increase | NS |
| lytM | glycyl-glycine endopeptidase | This study | in vivo invasion | Knockout | Increase | NS | |
| stress response | yjbH * | transcriptional regulator | [87] | in vivo invasion and survival | Knockout | Increase | NS |
| nfrA | NADPH-dependent oxidoreductase | This study | in vivo invasion | Knockout | Increase | NS | |
| B7H15_12300 | ClpA-like protein | This study | in vitro | Knockout | Increase | NS | |
| mnhD * | Na+/H+ antiporter subunit D | This study | in vivo invasion | Knockout | Increase | NS | |
| betT | choline transporter | This study | in vivo invasion | Knockout | Increase | Decrease | |
| peptidoglycan metabolism | fmhA | methicillin resistance protein | This study | in vivo invasion | Knockout | Increase | NS |
| femA | aminoacyltransferas | This study | in vitro | CRISPRi | Decrease | NS | |
| femB | aminoacyltransferase | This study | in vivo invasion | CRISPRi | Decrease | Decrease | |
| pbp2 | penicillin-binding protein 2 | This study | in vivo invasion | CRISPRi | Decrease | Decrease | |
| mutation repair | mutS | DNA mismatch repair protein | This study | in vivo invasion | Knockout | Increase | NS |
| unknown | murQ | N-acetylmuramic acid 6-phosphate etherase | [90] | in vivo invasion | Knockout | Increase | NS |
| rumA | 23S rRNA (uracil(1939)-C(5))-methyltransferase | This study | in vivo invasion | Knockout | Increase | NS | |
| rpoC | DNA-directed RNA polymerase subunit beta | This study | in vivo invasion | CRISPRi | NS | Increase | |
| B7H15_00625 | Hypothetical protein | This study | in vivo invasion | CRISPRi | Decrease | NS | |
| B7H15_08855 | RecD/TraA family helicase | This study | in vivo invasion | Knockout | Increase | NS | |
| B7H15_03805 | Hypothetical protein | This study | in vivo invasion | Knockout | Increase | Decrease | |
| B7H15_11520 | Hypothetical protein | This study | in vivo invasion | Knockout | Increase | NS |
* = gene with multiple functional categories
† NS = Not significant