Disease Information

General Information of the Disease (ID: DIS00025)

• Name: Bartonellosis
• ICD: ICD-11: 1C11

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.D95N
• Resistant Drug: Ciprofloxacin XR
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The mutation of bartonella bacilliformis at asp-95 residue of gyrA QRDR resulted in the production of ciprofloxacin resistant strains.

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.D90G
• Resistant Drug: Ciprofloxacin XR
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The mutation of bartonella bacilliformis at asp-90 residue of gyrA QRDR resulted in the production of ciprofloxacin resistant strains.

Tetracycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetW (TETW) [2]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• 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.

Investigative Drug(s) 1 drug(s) in total

Coumermycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [3]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.G124S
• Resistant Drug: Coumermycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• In Vitro Model: Bartonella bacilliformis strain CR1-CR12; 774
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain N99; 562
• In Vitro Model: Escherichia coli strain TOP10F'; 562
• Experiment for Molecule Alteration: DNA hybridizations assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: First, in 5 of the 12 coumermycin A1-resistant strains (CR1, CR2, CR6, CR8, and CR9), identical G-to-A transitions at base 370 of the 2,079-bp ORF resulted in a deduced Gly124-to-Ser (Gly124-Ser) substitution. Second, 4 of the 12 resistant strains (CR4, CR7, CR11, and CR12) carried a G-to-A transition at base 550 that resulted in a deduced Arg184-Gln substitution. The third loci at which lesions were detected occurred in the Thr214 codon, in which two different transitions were observed with two distinct deduced substitutions; the ACA-to-GCA transition resulted in a Thr214-Ala substitution (CR3), whereas the ACA-to-ATA transition resulted in a Thr214-Ile substitution (CR5, CR10). The MICs for GyrB mutants represented by strains CR3, CR4, and CR9 were determined to be 0.2 ug/ml, whereas the MIC for CR5 was 0.3 ug/ml. This suggests that a Thr214-Ile substitution confers a higher level of resistance than Thr214-Ala, Gly124-Ser, or Arg184-Gln, consistent with findings in B. burgdorferi.

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [3]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.R184Q
• Resistant Drug: Coumermycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• In Vitro Model: Bartonella bacilliformis strain CR1-CR12; 774
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain N99; 562
• In Vitro Model: Escherichia coli strain TOP10F'; 562
• Experiment for Molecule Alteration: DNA hybridizations assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: First, in 5 of the 12 coumermycin A1-resistant strains (CR1, CR2, CR6, CR8, and CR9), identical G-to-A transitions at base 370 of the 2,079-bp ORF resulted in a deduced Gly124-to-Ser (Gly124-Ser) substitution. Second, 4 of the 12 resistant strains (CR4, CR7, CR11, and CR12) carried a G-to-A transition at base 550 that resulted in a deduced Arg184-Gln substitution. The third loci at which lesions were detected occurred in the Thr214 codon, in which two different transitions were observed with two distinct deduced substitutions; the ACA-to-GCA transition resulted in a Thr214-Ala substitution (CR3), whereas the ACA-to-ATA transition resulted in a Thr214-Ile substitution (CR5, CR10). The MICs for GyrB mutants represented by strains CR3, CR4, and CR9 were determined to be 0.2 ug/ml, whereas the MIC for CR5 was 0.3 ug/ml. This suggests that a Thr214-Ile substitution confers a higher level of resistance than Thr214-Ala, Gly124-Ser, or Arg184-Gln, consistent with findings in B. burgdorferi.

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [3]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.Y214A
• Resistant Drug: Coumermycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• In Vitro Model: Bartonella bacilliformis strain CR1-CR12; 774
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain N99; 562
• In Vitro Model: Escherichia coli strain TOP10F'; 562
• Experiment for Molecule Alteration: DNA hybridizations assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: First, in 5 of the 12 coumermycin A1-resistant strains (CR1, CR2, CR6, CR8, and CR9), identical G-to-A transitions at base 370 of the 2,079-bp ORF resulted in a deduced Gly124-to-Ser (Gly124-Ser) substitution. Second, 4 of the 12 resistant strains (CR4, CR7, CR11, and CR12) carried a G-to-A transition at base 550 that resulted in a deduced Arg184-Gln substitution. The third loci at which lesions were detected occurred in the Thr214 codon, in which two different transitions were observed with two distinct deduced substitutions; the ACA-to-GCA transition resulted in a Thr214-Ala substitution (CR3), whereas the ACA-to-ATA transition resulted in a Thr214-Ile substitution (CR5, CR10). The MICs for GyrB mutants represented by strains CR3, CR4, and CR9 were determined to be 0.2 ug/ml, whereas the MIC for CR5 was 0.3 ug/ml. This suggests that a Thr214-Ile substitution confers a higher level of resistance than Thr214-Ala, Gly124-Ser, or Arg184-Gln, consistent with findings in B. burgdorferi.

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [3]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Molecule Alteration: Missense mutation; p.Y214I
• Resistant Drug: Coumermycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• In Vitro Model: Bartonella bacilliformis strain CR1-CR12; 774
• In Vitro Model: Escherichia coli strain N4177; 562
• In Vitro Model: Escherichia coli strain N99; 562
• In Vitro Model: Escherichia coli strain TOP10F'; 562
• Experiment for Molecule Alteration: DNA hybridizations assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: First, in 5 of the 12 coumermycin A1-resistant strains (CR1, CR2, CR6, CR8, and CR9), identical G-to-A transitions at base 370 of the 2,079-bp ORF resulted in a deduced Gly124-to-Ser (Gly124-Ser) substitution. Second, 4 of the 12 resistant strains (CR4, CR7, CR11, and CR12) carried a G-to-A transition at base 550 that resulted in a deduced Arg184-Gln substitution. The third loci at which lesions were detected occurred in the Thr214 codon, in which two different transitions were observed with two distinct deduced substitutions; the ACA-to-GCA transition resulted in a Thr214-Ala substitution (CR3), whereas the ACA-to-ATA transition resulted in a Thr214-Ile substitution (CR5, CR10). The MICs for GyrB mutants represented by strains CR3, CR4, and CR9 were determined to be 0.2 ug/ml, whereas the MIC for CR5 was 0.3 ug/ml. This suggests that a Thr214-Ile substitution confers a higher level of resistance than Thr214-Ala, Gly124-Ser, or Arg184-Gln, consistent with findings in B. burgdorferi.

References

• Ref 1: gyrA mutations in ciprofloxacin-resistant Bartonella bacilliformis strains obtained in vitro. Antimicrob Agents Chemother. 2003 Jan;47(1):383-6. doi: 10.1128/AAC.47.1.383-386.2003.
• Ref 2: Occurrence of the new tetracycline resistance gene tet(W) in bacteria from the human gut. Antimicrob Agents Chemother. 2000 Mar;44(3):775-7. doi: 10.1128/AAC.44.3.775-777.2000.
• Ref 3: Mutations in Bartonella bacilliformis gyrB confer resistance to coumermycin A1. Antimicrob Agents Chemother. 1998 Nov;42(11):2906-13. doi: 10.1128/AAC.42.11.2906.