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Table 2 Key effects of the measured gene expression differences after administration of IQ-143 compared to untreated S. epidermidis RP62A

From: Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidisand human cells

Concentration of IQ-143 (μM)

Enzymes affecteda

Effect on enzymesb

Phenotypic effectsc

0.16 μM

SERP0290-zinc-transport_efflux

Down-regulated

 
 

SERP0291-zinc-transporter_import

Down-regulated

40% biofilm inhibition

 

SERP0292-iron-dicitrate-transporter_import

Down-regulated

No growth inhibition

 

SERP2179-choline/betaine/carnitine-transp_efflux

Up-regulated

 

1.25 μM

SERP0290-zinc-transport_efflux

Down-regulated

 
 

SERP0291-zinc-transporter_import

Down-regulated

 
 

SERP0292-iron-dicitrate-transporter_import

Down-regulated

 
 

SERP0653-FGAM synthetase-rn:R04463

Down regulated

 
 

SERP0655-amidophosphoribosyltransferase-rn:R01072

Down-regulated

 
 

SERP0656-AIR synthetase-rn:R04208

Down-regulated

 
 

SERP0657-GAR formyltransferase-rn:R04325

Down-regulated

 
 

SERP0658-AICAR transformylase-rn:R04560

Down-regulated

~100% biofilm inhibition

 

SERP0659-glycinamide ribonucleotide synthetase-rn:R04144

Down-regulated

~100% growth inhibition

 

SERP0686-spermidine/putrescine-transport_import

Up-regulated

 
 

SERP0687-spermidine/putrescine-transport_import

Up-regulated

 
 

SERP0688-spermidine/putrescine-transport_import

Up-regulated

 
 

SERP0765-Uracil-permease-transport_import

Up-regulated

 
 

SERP0831-DNA polymerase-rn:R00375

Up-regulated

 
 

SERP0831-DNA polymerase-rn:R00376

Up-regulated

 
 

SERP0831-DNA polymerase-rn:R00378

Up-regulated

 
 

SERP0831-DNA polymerase-rn:R00379

Up-regulated

 
 

SERP0841-PNPase-rn:R00437

Up-regulated

 
 

SERP0841-PNPase-rn:R00439

Up-regulated

 
 

SERP1403-MultiDrug-transport_efflux

Up-regulated

 
 

SERP1802-cobalt/nickel-transport_efflux

Up-regulated

 
 

SERP1803-cobalt/nickel-transport_efflux

Up-regulated

 
 

SERP1944-MultiDrug-transport_efflux

Up-regulated

 
 

SERP1951-lipoprotein-transport_efflux/import

Down-regulated

 
 

SERP1952-macrolide-transport_efflux

Down-regulated

 
 

SERP1997-formate/nitrite-transport_efflux/import

Up-regulated

 
 

SERP2060-glyerol-transport_import

Up-regulated

 
 

SERP2179-choline/betaine/carnitine-transp_efflux

Up-regulated

 
 

SERP2186-ATP-sulfurylase;-rn:R00529

Down-regulated

 
 

SERP2283-phosphonate-transport_import

Up-regulated

 
 

SERP2289-MultiDrug-transport_efflux

Up-regulated

 
  1. aLocus tags are given first (SERP numbers), followed by abbreviated biochemical name and then KEGG reaction numbers (always starting with - m:R...). The effects on S. aureus USA300 were modeled (Table S20 in Additional file 1), are similar overall, and were validated by metabolite measurements. bDown-regulated means that gene expression was halved (or more then halved); up-regulated means that gene expression was doubled (or more than doubled). Specific values are given in Tables S5 and S6 in Additional file 1. All the enzymes with key changes in expression are part of the complete simulated metabolic model. cThe phenotypes are combination effects of the complete networks, not of single modes (see also Figure S2 in Additional file 1).