Molecule Information

General Information of the Molecule (ID: Mol00951)
Name
Elongation factor Tu (TUF) ,Enterococcus faecalis
Synonyms
EF-Tu; tuf; BH739_11460; BZK37_12225; D8N35_02625; DW084_10410; DW201_05310; EQ871_03935; EZ072_05275; I6H55_06960; I6I78_03065; I6I79_06190; NCTC12362_00252; NCTC4725_00358; NCTC7179_01977; RU99_GL000254; SAMN05216513_103246
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Molecule Type
Protein
Gene Name
tufA
Gene ID
15140833
Sequence
MAKEKFDRSKPHVNIGTIGHVDHGKTTLTAAITTVLSKKGLAQASAYDQIDGAPEERERG
ITISTAHVEYETEARHYAHVDCPGHADYVKNMITGAAQMDGAILVVSAADGPMPQTREHI
LLSRNVGVPYIVVFLNKMDMVDDEELLELVEMEVRDLLSEYDFPGDDVPVIAGSALKALE
GDASYEEKIMELMAAVDEYVPTPERDTDKPFMMPVEDVFSITGRGTVATGRVERGQVRVG
DEVEIVGIAEETAKTTVTGVEMFRKLLDYAEAGDNIGALLRGVAREDIQRGQVLAKAGTI
TPHTKFKAEVYVLTKEEGGRHTPFFTNYRPQFYFRTTDVTGVVELPEGTEMVMPGDNVTI
DVELIHPIAIEDGTRFSIREGGRTVGSGVVTSIQA
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Function
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
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Uniprot ID
A0A1L8SLM0_ENTCA
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Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Enterococcaceae
Genus: Enterococcus
Species: Enterococcus faecalis
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Investigative Drug(s)
2 drug(s) in total
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Elfamycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Enterococci faecalis infection [1]
Resistant Disease Enterococci faecalis infection [ICD-11: 1A00-1C4Z]
 Disease Info 
Resistant Drug Elfamycin
 Drug Info 
Molecule Alteration Expression
Inherence
Experimental Note Identified from the Human Clinical Data
In Vitro Model Enterococcus avium strain NCTC9938 33945
Enterococcus casseliflavus strain NCIMB11449 37734
Enterococcus durans strain NCTC8174 53345
Enterococcus faecalis strain NCTC775 1351
Enterococcus faecium strain NCTC 7171 1352
Enterococcus gallinarum strain NCTC11428 1353
Enterococcus hirae strain NCIMB6459 1354
Enterococcus raffinosus strain NCTC 12192 1989
Experiment for
Drug Resistance		 Agar dilution assay
Mechanism Description Among enterococci, susceptibility or resistance to elfamycins appears to be determined by the bacterial protein synthesis elongation factor EF-Tu. E.faecium, E.durans, and E.hirae were susceptible to the elfamycins, while isolates of E.faecalis and all other species tested were resistant. Elfamycin resistance in E.faecalis ATCC7080 was mediated by the intrinsic resistance of its EF-Tu.
Disease Class: Enterococci casseliflavus infection [1]
Resistant Disease Enterococci casseliflavus infection [ICD-11: 1A00-1C4Z]
 Disease Info 
Resistant Drug Elfamycin
 Drug Info 
Molecule Alteration Expression
Inherence
Experimental Note Identified from the Human Clinical Data
In Vitro Model Enterococcus avium strain NCTC9938 33945
Enterococcus casseliflavus strain NCIMB11449 37734
Enterococcus durans strain NCTC8174 53345
Enterococcus faecalis strain NCTC775 1351
Enterococcus faecium strain NCTC 7171 1352
Enterococcus gallinarum strain NCTC11428 1353
Enterococcus hirae strain NCIMB6459 1354
Enterococcus raffinosus strain NCTC 12192 1989
Experiment for
Drug Resistance		 Agar dilution assay
Mechanism Description Among enterococci, susceptibility or resistance to elfamycins appears to be determined by the bacterial protein synthesis elongation factor EF-Tu. E.faecium, E.durans, and E.hirae were susceptible to the elfamycins, while isolates of E.faecalis and all other species tested were resistant. Elfamycin resistance in E.faecalis ATCC7080 was mediated by the intrinsic resistance of its EF-Tu.
Kirromycin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Streptomyces cinnamoneus infection [2]
Resistant Disease Streptomyces cinnamoneus infection [ICD-11: 1C43.3]
 Disease Info 
Resistant Drug Kirromycin
 Drug Info 
Molecule Alteration Missense mutation
p.T378A
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Escherichia coli strain DH5alpha 668369
Escherichia coli strain JM109 83333
Streptomyces lividans strain 1326 1200984
Nocardia lactamdurans strain ATCC 27382 1913
Streptomyces cinnamoneus strain Tu89 53446
Streptomyces coelicolor strain M145 1902
Streptomyces glaucescens strain ETH 22794 1907
Experiment for
Molecule Alteration		 Southern hybridization assay
Mechanism Description The antibiotic kirromycin (kr) inhibits bacterial protein synthesis by binding to elongation factor Tu (EF-Tu). Streptomyces cinnamoneus and Nocardia lactamdurans, producers of antibiotics of the kr class, are known to possess an EF-Tu resistant to kr. Thr378, was mutated to the consensus Ala and the resulting mutant protein was sensitive to kr. Interestingly, it retained some activity (30% of the control) even at high kr concentrations.
References
Ref 1 Differential susceptibilities of enterococcal species to elfamycin antibiotics. J Clin Microbiol. 1994 Aug;32(8):2016-8. doi: 10.1128/jcm.32.8.2016-2018.1994.
Ref 2 Natural kirromycin resistance of elongation factor Tu from the kirrothricin producer Streptomyces cinnamoneus. Microbiology (Reading). 1997 Feb;143 ( Pt 2):617-624. doi: 10.1099/00221287-143-2-617.

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