Drug Information

Drug (ID: DG00118) and It's Reported Resistant Information

• Name: Tetracycline
• Synonyms: Amycin; Biocycline; Bristaciclin; Bristaciclina; Bristacycline; Ciclibion; Copharlan; Cyclomycin; Cytome; Dumocyclin; Enterocycline; Medocycline; Resteclin; Robitet; Sanclomycine; Tetrachel; Veracin; Bristaciclin alpha; Cefracycline suspension; Component of Tetrastatin; Sumycin syrup; Tetracycline Free Base; Tetracycline I; Tetracycline II; Tetracycline Monohydrochloride; Achromycin (naphthacene derivative); Achromycin, naphthacene derivative; Centet (base); Lemtrex (base); Liquamycin (Veterinary); Liquamycin, veterinary; Panmycin (TN); Piracaps (base); Polycycline (VAN); Polycycline (antibiotic); Polycycline, antibiotic; SK-Tetracycline; Sumycin (TN); T-125; Tetra-Co; Tetraciclina [INN-Spanish]; Tetracycline & VRC3375; Tetracycline (internal use); Tetracyclinum [INN-Latin]; Tetracyn (TN); Vetquamycin-324 (free base); Tetracycline (JAN/USP/INN); Tetracycline [USAN:INN:BAN:JAN]; Methyl-1,11-dioxo-2-naphthacenecarboxamide; 6-Methyl-1,11-dioxy-2-naphthacenecarboxamide
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (13 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [2]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
  Bacterial meningitis [ICD-11: 1D02]; [4]
  Bartonellosis [ICD-11: 1C11]; [3]
  Cholera [ICD-11: 1A00]; [5]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [6]
  Helicobacter pylori infection [ICD-11: DA60]; [7]
  Osteomyelitis/osteitis [ICD-11: FB84]; [8]
  Pharyngitis [ICD-11: CA02]; [9]
  Pneumonia [ICD-11: CA40]; [10]
  Salmonellosis [ICD-11: 1A09]; [11]
  Shigellosis [ICD-11: 1A02]; [12]
  Staphylococcus meningitis [ICD-11: 1B54]; [13]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (6 diseases)
  Actinomycetoma [ICD-11: 1C43]; [14]
  Bacillus infection [ICD-11: 1C4Y]; [15]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [16]
  Campylobacteriosis [ICD-11: 1C40]; [17]
  Clostridioides difficile intestinal infection [ICD-11: 1A04]; [18]
  Pasteurellosis [ICD-11: 1B99]; [19]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C22H24N2O8
• IsoSMILES: C[C@@]1([C@H]2C[C@H]3[C@@H](C(=O)C(=C([C@]3(C(=O)C2=C(C4=C1C=CC=C4O)O)O)O)C(=O)N)N(C)C)O
• InChI: 1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25-26,29,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1
• InChIKey: NWXMGUDVXFXRIG-WESIUVDSSA-N
• PubChem CID: 54675776
• ChEBI ID: CHEBI:27902
• TTD Drug ID: D08NQZ
• VARIDT ID: DR00127
• INTEDE ID: DR1568
• DrugBank ID: DB00759

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Cholera [ICD-11: 1A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Dihydrofolate reductase (DHFR) [5]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae PG149a; 666
• In Vitro Model: Vibrio cholerae PL61; 666
• In Vitro Model: Vibrio cholerae PL78/6; 666
• In Vitro Model: Vibrio cholerae PL91; 666
• In Vitro Model: Vibrio cholerae PL141; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of dfrA1 lead to drug resistance.

Key Molecule: Dihydrofolate reductase (DHFR) [5]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae PG170; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of dfrA15 lead to drug resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Major facilitator superfamily (MFS) [20]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: E1 Tor C6706; 1124478
• In Vivo Model: Infant mouse colonisation; Mus musculus
• Experiment for Molecule Alteration: Lux reporters assay
• Experiment for Drug Resistance: Plate counting assay
• Mechanism Description: Deletion of all five mfs genes results in increased susceptibility to tetracycline and the antimicrobial agents present in crud.

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein Tet (TETW/N/W) [21]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli EPI-300; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Tet(W/N/W) encodes mosaic ribosomal protection(since tetracyclines bind to the 30S ribosomal subunit to inhibit protein translation) and induces resistance.

Key Molecule: Tetracycline resistance protein TetM (TETM) [22]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Enterococci infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis OG1RF:pCF10; 474186
• In Vitro Model: Enterococcus faecalis OG1SSp; 1351
• In Vivo Model: House fly model; House fly
• Experiment for Molecule Alteration: Bacterial colonies count assay
• Experiment for Drug Resistance: Broth dilution assay
• Mechanism Description: Tetracycline resistance of Musca domestica occurred by transferring the plasmid transduced with tetracycline resistance gene TETM of Enterococcus into Musca domestica.

Key Molecule: Tetracycline resistance protein TetW (TETW) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Butyrivibrio fibrisolvens infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bifidobacterium longum strain F10; 216816
• In Vitro Model: Bifidobacterium longum strain F5; 216816
• In Vitro Model: Bifidobacterium longum strain F8; 216816
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.23; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.230; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk214; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk51; 831
• In Vitro Model: Fusobacterium prausnitzii strain k10; 853
• In Vitro Model: Mitsuokella multiacidus strain 46/5(2); 52226
• In Vitro Model: Mitsuokella multiacidus strain P208-58; 52226
• In Vitro Model: Selenomonas ruminantium strain FB32; 971
• In Vitro Model: Selenomonas ruminantium strain FB322; 971
• In Vitro Model: Selenomonas ruminantium strain FB34; 971
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.

Key Molecule: Tetracycline resistance protein TetW (TETW) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Selenomonas ruminantium infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bifidobacterium longum strain F10; 216816
• In Vitro Model: Bifidobacterium longum strain F5; 216816
• In Vitro Model: Bifidobacterium longum strain F8; 216816
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.23; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.230; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk214; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk51; 831
• In Vitro Model: Fusobacterium prausnitzii strain k10; 853
• In Vitro Model: Mitsuokella multiacidus strain 46/5(2); 52226
• In Vitro Model: Mitsuokella multiacidus strain P208-58; 52226
• In Vitro Model: Selenomonas ruminantium strain FB32; 971
• In Vitro Model: Selenomonas ruminantium strain FB322; 971
• In Vitro Model: Selenomonas ruminantium strain FB34; 971
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.

Key Molecule: Tetracycline resistance protein TetW (TETW) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mitsuokella multiacidus infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bifidobacterium longum strain F10; 216816
• In Vitro Model: Bifidobacterium longum strain F5; 216816
• In Vitro Model: Bifidobacterium longum strain F8; 216816
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.23; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.230; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk214; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk51; 831
• In Vitro Model: Fusobacterium prausnitzii strain k10; 853
• In Vitro Model: Mitsuokella multiacidus strain 46/5(2); 52226
• In Vitro Model: Mitsuokella multiacidus strain P208-58; 52226
• In Vitro Model: Selenomonas ruminantium strain FB32; 971
• In Vitro Model: Selenomonas ruminantium strain FB322; 971
• In Vitro Model: Selenomonas ruminantium strain FB34; 971
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.

Key Molecule: Tetracycline resistance protein TetW (TETW) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Fusobacterium prausnitzii infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bifidobacterium longum strain F10; 216816
• In Vitro Model: Bifidobacterium longum strain F5; 216816
• In Vitro Model: Bifidobacterium longum strain F8; 216816
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.23; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.230; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk214; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk51; 831
• In Vitro Model: Fusobacterium prausnitzii strain k10; 853
• In Vitro Model: Mitsuokella multiacidus strain 46/5(2); 52226
• In Vitro Model: Mitsuokella multiacidus strain P208-58; 52226
• In Vitro Model: Selenomonas ruminantium strain FB32; 971
• In Vitro Model: Selenomonas ruminantium strain FB322; 971
• In Vitro Model: Selenomonas ruminantium strain FB34; 971
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.

Key Molecule: Tetracycline resistance protein TetS (TETS) [23], [24]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis JH2-2; 1351
• In Vitro Model: Enterococcus spp. Isolates; 35783
• In Vitro Model: Streptococcus milleri isolates; 33040
• In Vitro Model: Streptococcus sanguis isolates; 1305
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: TetS confers tetracycline and minocycline resistance by ribosomal protection.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: acrB-acrA (Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: High-throughput sequencing assay
• Mechanism Description: Relative abundance of ARGs was significantly increased under high oxytetracycline concentration. Of the 36 ARG-carrying contigs in the OTC-25 plasmidome, 20 were matched in the NCBI Plasmid Genome Database, with 17 carrying multiple ARGs (carrying >= 2 ARGs), including gene combinations of pecM-tetA-tetR-qnrS1, tet31-tetR(31) (tetR(31), which is used to regulate the expression of tet31 gene, is one kind of tetR (tetracycline repressor gene)), floR-sul1, strA-strB, acrB-acrA, ATP-binding cassette transporter (ABC transporter)-ABC transporter, and mexC.

Key Molecule: Protein PecM (PeECM) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: High-throughput sequencing assay
• Mechanism Description: Relative abundance of ARGs was significantly increased under high oxytetracycline concentration. Of the 36 ARG-carrying contigs in the OTC-25 plasmidome, 20 were matched in the NCBI Plasmid Genome Database, with 17 carrying multiple ARGs (carrying >= 2 ARGs), including gene combinations of pecM-tetA-tetR-qnrS1, tet31-tetR(31) (tetR(31), which is used to regulate the expression of tet31 gene, is one kind of tetR (tetracycline repressor gene)), floR-sul1, strA-strB, acrB-acrA, ATP-binding cassette transporter (ABC transporter)-ABC transporter, and mexC.

Key Molecule: Major facilitator superfamily MFS_1 (TETV) [25], [26], [27]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium abscessus OS11; 36809
• In Vitro Model: Mycobacterium abscessus OS13; 36809
• In Vitro Model: Mycobacterium fortuitum OS2/7; 1766
• In Vitro Model: Mycobacterium fortuitum OS21; 1766
• In Vitro Model: Mycobacterium fortuitum OS24; 1766
• In Vitro Model: Mycobacterium fortuitum OS25; 1766
• In Vitro Model: Mycobacterium fortuitum OS28; 1766
• In Vitro Model: Mycobacterium fortuitum OS30; 1766
• In Vitro Model: Mycobacterium fortuitum OS8; 1766
• In Vitro Model: Mycobacterium fortuitum OS9; 1766
• In Vitro Model: Mycobacterium fortuitum TR-1378; 1766
• In Vitro Model: Mycobacterium mucogenicum OS11; 56689
• In Vitro Model: Mycobacterium peregrinum OS2/8; 43304
• In Vitro Model: Mycobacterium smegmatis OS1; 1772
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: Tetracycline/multidrug efflux pumps Tet(V) and Tap may belong to this intrinsic resistome as they have been so far found only in certain RGM species.tet(V) and tap, both encode mycobacterial efflux pumps, including species where these genes have never been evidenced before.

Key Molecule: Tetracycline resistance protein class A (TETA) [25], [28]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli LM317; 562
• In Vitro Model: Escherichia coli TB1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The bacterial tetracycline-resistance determinant from Tn10 encodes a 43 kDa membrane protein, TetA, responsible for active efflux of tetracyclines.

Key Molecule: ARE-ABC-F family resistance factor PoxtA (POXTA) [29]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• In Vitro Model: Enterococcus faecalis JH2-2; 1351
• In Vitro Model: Escherichia coli Mach1 T1R; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth dilution test assay
• Mechanism Description: The poxtA gene encodes a protein that is 32% identical to OptrA and exhibits structural features typical of the F lineage of the ATP-binding cassette (ABC) protein superfamily that cause antibiotic resistance by ribosomal protection.

Key Molecule: Tetracycline resistance protein class A48 (TETA48) [30]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Paenibacillus sp. LC231; 1120679
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Two predicted ABC-transporters that confer resistance to tetracycline (TetAB(48)) and tiamulin (TaeA).

Key Molecule: Tetracycline resistance protein tet(59) (TET59) [21]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli EPI-300; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Tet(59) is preceded by a homolog of the tetracycline repressor tetR typically found upstream of tet genes encoding efflux pumps and include the two palindromic operator sequences present in all regulatory regions of the tet(A)-tet(R) family (33), suggesting that tet(59) probably belongs to the efflux pump family.

Key Molecule: Tetracycline efflux protein TetA (TETA) [31]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Corynebacterium glutamicum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum ATCC 13032; 196627
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: Tet33 causes tetracycline resistance by regulating tetracycline efflux.

Key Molecule: Tetracycline efflux Na+/H+ antiporter family transporter Tet(35) (TEE35) [16]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Vibrio harveyi infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli TOP 10; 83333
• In Vitro Model: Vibrio harveyi M3.4L; 669
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Agar dilution technique assay
• Mechanism Description: We describe the cloning and characterization of two tetracycline resistance determinants from V. harveyi strain M3.4L. The second determinant, cloned as a 3,358-bp fragment in pATJ1, contains two open reading frames, designated tet35 and txr. tet35 encodes a 369-amino-acid protein that was predicted to have nine transmembrane regions. Tetracycline accumulation studies indicate that Escherichia coli carrying tet35 and txr can function as an energy-dependent tetracycline efflux pump but is less efficient than TetA.

Key Molecule: Tetracycline resistance protein class A (TETA) [32]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Corynebacterium striatum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. The tetracycline and oxacillin resistance region is part of a DNA segment structurally similar to the chromosome of the human pathogen Mycobacterium tuberculosis. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

Key Molecule: Tetracycline resistance protein class A (TETA) [32]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Corynebacterium glutamicum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. Both resistance genes are located on mobile DNA elements that are capable of transposition into the chromosome of the non-pathogenic soil bacteriumC. glutamicum. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

Key Molecule: Tetracycline efflux protein tet(L) (TETL) [25], [33]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain Sk1592; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Gradient plate method assay
• Mechanism Description: The class L determinant, on the other hand, does not prevent the inhibition of protein synthesis in S. faecalis but rather decreases tetracycline uptake.The class L (TetL) tetracycline resistance determinant from streptococci specified resistance and an energy-dependent decreased accumulation of tetracycline in both Streptococcus faecalis and Escherichia coli.

Clostridioides difficile intestinal infection [ICD-11: 1A04]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetM (TETM) [18]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Of the resistance mechanisms, C. difficile produces ribosomal protection protein that impedes the attachment of the drug to a ribosome. The TetM protein that functions as ribosomal protectant has been identified in TET-resistant C. difficile strains, whereas the presence of other Tet proteins such as Tet(W) and Tet(44) has also been recognized. The TetM exhibits homology to EF-G and shares the same binding region in a ribosome. The binding of the TetM protein to a ribosome accompanying with the GTP hydrolysis allows conformational change of the ribosome, resulting in the dissociation of TET from its binding site. Cellular protein synthesis is then recovered through the binding of EF-G after the release of hydrolysed TetM.

Key Molecule: Tetracycline resistance protein TetW (TETW) [18]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Of the resistance mechanisms, C. difficile produces ribosomal protection protein that impedes the attachment of the drug to a ribosome. The TetM protein that functions as ribosomal protectant has been identified in TET-resistant C. difficile strains, whereas the presence of other Tet proteins such as Tet(W) and Tet(44) has also been recognized. The TetM exhibits homology to EF-G and shares the same binding region in a ribosome. The binding of the TetM protein to a ribosome accompanying with the GTP hydrolysis allows conformational change of the ribosome, resulting in the dissociation of TET from its binding site. Cellular protein synthesis is then recovered through the binding of EF-G after the release of hydrolysed TetM.

Key Molecule: Ribosomal tetracycline resistance protein tet (TET(44)) [18]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Human immunodeficiency virus infection [ICD-11: 1C62.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Of the resistance mechanisms, C. difficile produces ribosomal protection protein that impedes the attachment of the drug to a ribosome. The TetM protein that functions as ribosomal protectant has been identified in TET-resistant C. difficile strains, whereas the presence of other Tet proteins such as Tet(W) and Tet(44) has also been recognized. The TetM exhibits homology to EF-G and shares the same binding region in a ribosome. The binding of the TetM protein to a ribosome accompanying with the GTP hydrolysis allows conformational change of the ribosome, resulting in the dissociation of TET from its binding site. Cellular protein synthesis is then recovered through the binding of EF-G after the release of hydrolysed TetM.

Salmonellosis [ICD-11: 1A09]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug transporter MdfA (MDFA) [11]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Salmonella enterica infection [ICD-11: 1A09.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enterica serovar Typhimurium ATCC 14028s; 588858
• Experiment for Molecule Alteration: Quantitative real-time PCR
• Experiment for Drug Resistance: L agar plate method assay
• Mechanism Description: Overexpression or overproduction of mdfA confers drug resistance.

Staphylococcus meningitis [ICD-11: 1B54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tetracycline efflux MFS transporter Tet(38) (TET38) [13]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: DNA microarray hybridization assay
• Experiment for Drug Resistance: Serial twofold agar dilutions assay
• Mechanism Description: MgrA was an indirect regulator of tet38 expression. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) [13]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: DNA microarray hybridization assay
• Experiment for Drug Resistance: Serial twofold agar dilutions assay
• Mechanism Description: MgrA was an indirect regulator of tet38 expression. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain.

Pasteurellosis [ICD-11: 1B99]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Tetracycline repressor protein class H (TETR) [19]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Pasteurella multocida infection [ICD-11: 1B99.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Pasteurella multocida 36950; 1075089
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The analysis of one representative P. multocida isolate identified an 82 kb integrative and conjugative element (ICE) integrated into the chromosomal DNA. This ICE, designated ICEPmu1, harboured 11 resistance genes, which confer resistance to streptomycin/spectinomycin (aadA25), streptomycin (strA and strB), gentamicin (aadB), kanamycin/neomycin (aphA1), tetracycline [tetR-tet(H)], chloramphenicol/florfenicol (floR), sulphonamides (sul2), tilmicosin/clindamycin [erm(42)] or tilmicosin/tulathromycin [msr(E)-mph(E)].

Bartonellosis [ICD-11: 1C11]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetW (TETW) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bifidobacterium longum strain F10; 216816
• In Vitro Model: Bifidobacterium longum strain F5; 216816
• In Vitro Model: Bifidobacterium longum strain F8; 216816
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.23; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain 1.230; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk214; 831
• In Vitro Model: Butyrivibrio fibrisolvens strain Jk51; 831
• In Vitro Model: Fusobacterium prausnitzii strain k10; 853
• In Vitro Model: Mitsuokella multiacidus strain 46/5(2); 52226
• In Vitro Model: Mitsuokella multiacidus strain P208-58; 52226
• In Vitro Model: Selenomonas ruminantium strain FB32; 971
• In Vitro Model: Selenomonas ruminantium strain FB322; 971
• In Vitro Model: Selenomonas ruminantium strain FB34; 971
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.

Campylobacteriosis [ICD-11: 1C40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Ribosomal tetracycline resistance protein tet(44) (TET44) [17]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Campylobacter fetus infection [ICD-11: 1C40.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli S17-1 Lambdapir; 1227813
• Experiment for Molecule Alteration: Illumina/Solexa sequencing assay
• Experiment for Drug Resistance: Broth microdilution assay
• Mechanism Description: The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class of proteins that confers resistance to tetracycline and minocycline by ribosomal protection.

Actinomycetoma [ICD-11: 1C43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Oxytetracycline resistance efflux MFS transporter OtrB (OTRB) [34]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces rimosus infection [ICD-11: 1C43.12]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces rimosus strain; 1927
• Mechanism Description: The sequence of the tetracycline resistance gene designated tet347 from the tetracycline-producing organism Streptomyces rimosus (strain PG3) predicted a protein of 347 amino acids (GenBank accession no. M20370). The tcrC gene (also called tcr3; GenBank accession no. D38215) from chlorotetracycline-producing S. aureofaciens encoded a 512-residue putative tetracycline efflux protein which, starting at residue 222, was 43% identical to the Tet347 protein.

Key Molecule: Protein tcr3 (TCR3) [14]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces aurebyaciens infection [ICD-11: 1C43.2]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain XLI-Blue; 562
• In Vitro Model: Streptomyces aureofaciens strain NRRL3203; 1894
• In Vitro Model: Streptomyces lividans strain Tk23; 1916
• Experiment for Molecule Alteration: Northern blotting analysis
• Mechanism Description: The analysis of the nucleotide sequence of the 2.8-kb BamHI fragment containing tcrC gene showed that the predicted tcrC gene product is a protein consisting of 512 amino acids. The deduced amino acid sequence had a high level identity with that of the self-defense gene (tet347) of Streptomyces rimosus, known to mediate oxytetracycline efflux. The tcrC gene-inactivated strains generated from strain NRRL3203 by gene replacement had a 90% decrease in the level of resistance to tetracycline and the antibiotic productivity when compared with the parental strain.

Bacillus infection [ICD-11: 1C4Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides uniformis infection [ICD-11: 1C4Y.11]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides distasonis infection [ICD-11: 1C4Y.5]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Bacterial meningitis [ICD-11: 1D02]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tetracycline resistance protein TetU (TETU) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Enterococcus faecium meningitis [ICD-11: 1D01.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Enterococcus faecalis strain JH2-2; 1320322
• In Vitro Model: Enterococcus faecium strain CH2; 1352
• Experiment for Molecule Alteration: DNA Hybridization assay
• Experiment for Drug Resistance: Tube dilution method assay
• Mechanism Description: PkQ10, a 1.9-kb plasmid carrying a novel Tc resistance determinant, was isolated from one of the isolates. The nucleotide sequence of this plasmid revealed an open reading frame corresponding to an 11.8-kDa protein and containing 105 amino acid residues. There was some limited similarity between this protein andtet(M),tet(O),tet(Q),tet(S),tetB(P), andotr(A), which overlapped, but did not include, the consensus GTP-binding sequences. The low-level, Tc-resistant determinant of pkQ10, namedtet(U), does not appear to correspond to any other known Tc resistance determinant.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug efflux SMR transporter (ABES) [35]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• Experiment for Molecule Alteration: Fluorometric efflux assay
• Experiment for Drug Resistance: Broth dilution assay
• Mechanism Description: The abeS gene product conferred resistance to various antimicrobial compounds through an efflux mechanism.

Key Molecule: Tetracycline efflux protein (TET41) [36]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Serratia marcescens infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli JM109; 562
• Experiment for Molecule Alteration: DNA sequencing and protein and phylogenetic assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet 41 is a tetracycline-specific efflux pump, which lead to drug resistance.

Key Molecule: Tetracycline efflux proteintet(39) (TET39) [10]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter sp. LUH5605; 309867
• Experiment for Molecule Alteration: DNA multiple alignment assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Tet39 produces drug resistance through the action of nonspecific efflux pump.

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