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  • Transcriptomic and metabolic alterations in fosmidomycin-treated parasite
Transcriptomic and metabolic alterations in fosmidomycin-treated parasite
Tewari SG, Rajaram K, Swift RP, Reifman J, Prigge ST, Wallqvist A. Metabolic survival adaptations of  exposed to sub-lethal doses of fosmidomycin. Antimicrob Agents Chemother. 2021 AAC.02392-20. PMID: 33495219.
Fold change in average abundance of metabolites in infected relative to uninfected erythrocyte cultures under untreated and fosmidomycin-treated conditions
Main pathway Subordinate pathway Metabolite FCIDC (SD)*
CTL† FOS
Amino Acid metabolism  Alanine aspartate N-Acetylasparagine  1.63 (0.14)  0.44 (0.03)
Carbohydrate metabolism Glycolysis 2-Phosphoglycerate 0.29 (0.08) 1.50 (0.30)
Pentose phosphate shunt Arabitol/xylitol 0.22 (0.02)  0.04 (0.01)
Lipid  Lysophospholipid 1-Oleoyl-GPS (18:1) 1.49 (0.19)  6.80 (1.10)
Monoacylglycerol 1-Oleoylglycerol (18:1) 2.59 (0.37) 0.88 (0.07)
Phospholipid Phosphoethanolamine 13.6 (1.14) 3.87 (0.51)
Sphingolipid Lactosylceramide (d18:1/24:1)  3.03 (0.20) 1.01 (0.18)
Nucleotide  Purine metabolism Deoxyadenosine monophosphate 0.74 (0.04) 2.16 (0.27)
Guanine 4.92 (0.89) 1.17 (0.04)
Inosine 1.30 (0.07) 0.40 (0.02)
Xanthine  3.83 (0.38) 1.03 (0.03)
Pyrimidine metabolism Cytidine 0.48 (0.08) 5.18 (0.42)
Peptide  Dipeptide Phenylalanylalanine 0.52 (0.05)  0.17 (0.02)
PFID New Annotation peak   h of IDC Fcgene (SD) EC# Transcript
PF3D7_1319100 ubiquitin carboxyl-terminal hydrolase mindy, putative 0 0 1.00 (0.16) 3.4.19.12
PF3D7_1437900
HSP40, subfamily A 20 23 1.32 (0.21)
PF3D7_0322000
peptidyl-prolyl cis-trans isomerase 23 25 1.84 (0.54) 5.2.1.8
PF3D7_1113100
protein tyrosine phosphatase 0 0 1.03 (0.14) 3.1.3.48
PF3D7_1231100
ras-related protein Rab-2 3 18 4.01 (4.22) 3.6.5.2
PF3D7_0106800
ras-related protein Rab-5C 35 35 2.21 (0.65) 3.6.5.2
PF3D7_1320600
ras-related protein Rab-11A 48 48 1.31 (0.32) 3.6.5.2
PF3D7_1340700
ras-related protein Rab-11B 36 37 0.93 (0.22) 3.6.5.2
PF3D7_0807300
ras-related protein Rab-18 20 24 0.94 (0.37) 3.6.5.2
PF3D7_0513800
ras-related protein Rab-1A 28 31 0.98 (0.28) 3.6.5.2
PF3D7_0512600 ras-related protein Rab-1B 8 40 3.05 (0.76) 3.6.5.2
PF3D7_0211200
ras-related protein Rab-5A 30 34  0.80 (0.27) 3.6.5.2
PF3D7_1310600
ras-related protein Rab-5B secretory complex protein 61 alpha 41 41 0.98 (0.17) 3.6.5.2
PF3D7_1144900
ras-related protein Rab-6 39 41 1.34 (0.40) 3.6.5.2
PF3D7_0903200
ras-related protein RAB7 32 32 0.76 (0.10) 3.6.5.2
PF3D7_0910600
SNARE protein 48 48  1.47 (0.23)
PF3D7_1324700 SNARE protein, putative 40 7 1.23 (0.40)
Hour (tpeak) of intraerythrocytic developmental cycle (IDC) when the gene was maximally expressed. † The fold change value (FCgene) of a gene was computed as the ratio of the average gene-expression level under the treated condition to that under the untr
PFID New peak   h of IDC Fcgene (SD) EC# Transcript
PF3D7_0707400
AAA family ATPase, putative 15 31 3.29 (2.79)
PF3D7_1426500
ABC transporter G family member 2 20 39 0.81 (0.21)
PF3D7_1037300
ADP, ATP carrier protein 1, aac1 13 23 0.87 (0.20)
PF3D7_0515500 gametogenesis essential protein 1, putative, gep1 0 38 0.70 (0.22)
PF3D7_0523800 divalent metal transporter, putative 0 6 1.88 (0.36)
PF3D7_0821800 protein transport protein SEC61 subunit beta 9 15 1.76 (0.55)
PF3D7_0622300 vacuolar transporter chaperone, putative 0 26 0.51 (0.11)
PF3D7_0721900 V-type ATPase V0 subunit e, putative 17 41 1.32 (0.33)
PF3D7_1354400 V-type proton ATPase 21 kDa proteolipid subunit, putative 17 40  1.05 (0.13) 3.6.3.14
PF3D7_1341900
V-type proton ATPase subunit D, putative 0 16  3.13 (1.98) 3.6.3.14
PF3D7_0934500 V-type proton ATPase subunit E, putative 0 16 2.01 (0.98) 3.6.3.14
Hour (tpeak) of intraerythrocytic developmental cycle (IDC) when the gene was maximally expressed. † The fold change value (FCgene) of a gene was computed as the ratio of the average gene-expression level under the treated condition to that under the untreated condition. Abbreviations: CTL, untreated; FOS, fosmidomycin-treated; SD,  standard deviation.
Genes encoding ATPases and transporters
PFID New peak   h of IDC Fcgene (SD) EC# Transcript
PF3D7_0707400
AAA family ATPase, putative 15 31 3.29 (2.79)
PF3D7_1426500
ABC transporter G family member 2 20 39 0.81 (0.21)
PF3D7_1037300
ADP, ATP carrier protein 1, aac1 13 23 0.87 (0.20)
PF3D7_0515500 gametogenesis essential protein 1, putative, gep1 0 38 0.70 (0.22)
PF3D7_0523800 divalent metal transporter, putative 0 6 1.88 (0.36)
PF3D7_0821800 protein transport protein SEC61 subunit beta 9 15 1.76 (0.55)
PF3D7_0622300 vacuolar transporter chaperone, putative 0 26 0.51 (0.11)
PF3D7_0721900 V-type ATPase V0 subunit e, putative 17 41 1.32 (0.33)
PF3D7_1354400 V-type proton ATPase 21 kDa proteolipid subunit, putative 17 40  1.05 (0.13) 3.6.3.14
PF3D7_1341900
V-type proton ATPase subunit D, putative 0 16  3.13 (1.98) 3.6.3.14
PF3D7_0934500 V-type proton ATPase subunit E, putative 0 16 2.01 (0.98) 3.6.3.14
Hour (tpeak) of intraerythrocytic developmental cycle (IDC) when the gene was maximally expressed. The foldchange value (FCgene) of a gene was computed as the ratio of the average gene-expression level under the treated condition to that under the untreated condition. Abbreviations: CTL, untreated; FOS, fosmidomycin treated; SD,  standard deviation.
Genes involved in translational initiation
PFID New peak   h of IDC Fcgene (SD) EC# Transcript
Initiation factors
PF3D7_1010600 eukaryotic translation initiation factor 2 subunit beta, putative 13 23 1.53 (0.28)
PF3D7_1410600 eukaryotic translation initiation factor 2 subunit gamma, putative 6 18 2.29 (0.53)
PF3D7_0918300 eukaryotic translation initiation factor 3 subunit F, putative 10 19 1.86 (0.51)
PF3D7_0815600 eukaryotic translation initiation factor 3 subunit G, putative 0 12 1.94 (1.07)
PF3D7_1468700
eukaryotic initiation factor 4A helicase 45 8 22 1.32 (0.24) 3.6.4.12
PF3D7_1204300
eukaryotic translation initiation factor 5A 18 24 1.48 (0.32)
Methyl-group requiring enzymes
PF3D7_1415800
ribosomal RNA small subunit methyltransferase a1 13 20 1.47 (0.44) 2.1.1.183
PF3D7_1313200
methionyl-tRNA formyltransferase, putative 24 32 1.26 (1.01) 2.1.2.9
PF3D7_1235500 mRNA methyltransferase, putative, METTL14 19 25 1.18 (0.14) 2.1.1.62
PF3D7_0525600 RNA methyltransferase, putative 24 47 1.18 (0.16) 2.1.1.56
PF3D7_1407500 multifunctional methyltransferase subunit TRM112, putative 0 15 0.75 (0.18) 2.1.1.32
PF3D7_1406900 radical SAM protein, putative 22 42  1.03 (0.23)
PF3D7_0622500 RNA methyltransferase, putative 9 15 0.68 (0.17) 2.1.1.-
PF3D7_1319300 tRNA (guanine(26)-n(2))-dimethyltransferase, putative 11 16 0.75 (0.12) 2.1.1.32
PF3D7_1343200 tRNA guanosine-2'-O-methyltransferase, putative 11 41 1.22 (0.24) 2.1.1.34
PF3D7_1120500 tRNA nucleotidyltransferase, putative 7 14 1.20 (0.49) 2.7.7.72
Ribosomal proteins
PF3D7_0112300 18S ribosomal RNA 4 15  0.95 (0.20)
PF3D7_1317800 40S ribosomal protein S19 5 15 2.32 (1.28)
PF3D7_0306900 40S ribosomal protein S23, putative 0 15 1.39 (0.83)
PF3D7_0725800 5.8S ribosomal RNA 0 39 0.91 (0.06)
PF3D7_1424400 60S ribosomal protein L7-3, putative 9 14 2.04 (0.65)
PF3D7_1338200 60s ribosomal protein l6, putative 7 15 3.05 (1.42)
PF3D7_API01800 apicoplast ribosomal protein L16 7 32 2.21 (1.31)
PF3D7_API00100 apicoplast ribosomal protein S4 0 31 0.62 (0.23)
PF3D7_1457700 large ribosomal subunit nuclear export factor, putative 0 15 1.41 (0.13)
Gnes involved in translational regulation
PFID New peak   h of IDC Fcgene (SD) EC# Transcript
RNA-binding proteins
PF3D7_1359400
Cugbp Elav-like family member 1 11 15 1.13 (0.21)
PF3D7_1409800 CUGBP Elav-like family member 2 0 19 2.35 (1.65)
PF3D7_1346300
DNA/RNA-binding protein Alba 2 0 48 1.68 (0.79)
PF3D7_1006200
DNA/RNA-binding protein Alba 3 22 25 0.83 (0.15)
PF3D7_0417100 mRNA-binding protein PUF2 0 0 0.48 (0.27)
CNOT complex
PF3D7_0107200
ccr4 domain-containing protein 3, putative 13 26 1.12 (0.66)
PF3D7_1434000
CCR4-associated factor 16, putative 0 15 6.85 (5.67)
PF3D7_1128600 CCR4-NOT transcription complex subunit 2, putative 0 29 0.96 (0.32)
PF3D7_1235300 CCR4-NOT transcription complex subunit 4, putative 0 4 0.94 (0.14)
PF3D7_1006100 CCR4-NOT transcription complex subunit 5, putative 5 10 1.34 (1.00)
PF3D7_0507600 protein caf40, putative 8 14 1.88 (0.45)
mRNA decapping
PF3D7_1308900 mRNA-decapping enzyme 2, putative 10 15  0.80 (0.13)
PF3D7_0819900 U6 snRNA-associated Sm-like protein LSm3, putative 11 25  0.98 (0.22)
PF3D7_1443300 U6 snRNA-associated Sm-like protein LSm5, putative 8 11 5.19 (4.48)
PF3D7_1209200 U6 snRNA-associated Sm-like protein LSm7, putative 14 24 1.28 (0.36)
PF3D7_0829300 U6 snRNA-associated Sm-like protein LSm8, putative 12 22 1.62 (0.55)
mRNA degradation
PF3D7_0209200 exosome complex component MTR3, putative 8 11 1.50 (0.62) 3.1.16.1
PF3D7_1106300 5'-3' exoribonuclease 1, putative 24 30 0.75 (0.25) 3.1.4.1
PF3D7_0720000 exosome complex component CSL4, putative 8 12 0.75 (0.13) 3.1.13.1
PF3D7_0909900 helicase ski2w 0 5 1.24 (0.09) 3.6.4.13
Hour (tpeak) of intraerythrocytic developmental cycle (IDC) when the gene was maximally expressed. The fold change value (FCgene) of a gene was computed as the ratio of the average gene-expression level under the treated condition to that under the untrea
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