In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease

Figures & data

Figure 1 The efficacy of cephalosporins determined by BacTiter-Glo Assay.

Notes: Effect of drugs on Borrelia cell viability was studied with drugs (cefoxitin, cefamandole, cefuroxime, and cefapirin) on CA8 strain. The control has no drug. The results represent mean ± SD.

Table 1 MIC and MBC values (in µM) of the tested compounds on bacterial strains CA8, JLB31, and NP40

Compounds	CA8	JLB31	NP40
MIC values
Cefamandole	1.25	1.25	2.5
Cefapirin	2.5	5	10
Cefoxitin	0.625	0.625	1.25
Cefuroxime	1.25	2.5	5
MBC values
Cefamandole	20	40	20
Cefapirin	20	10	.160
Cefoxitin	5	5	2.5
Cefuroxime	10	20	10

Abbreviations: MBC, minimum bactericidal concentration; MIC, minimum inhibitory concentration.

Table 2 Therapeutic effectiveness of tested compounds in Borrelia burgdorferi-infected C3H mice

Drug name	Concentration of drugs	No of mice infected	No of mice treated	No of mice cured/no of mice given
Cefoxitin	20 mg/kg	3	3	3/3
Ceftriaxone	50 mg/kg	3	3	3/3
Saline (control)		3	3	0/3

Table 3 Predicted docking scores of cephalosporins with Borrelia burgdorferi SecA-PBP and OspE

Protein name	Pdb I.D.	Binding affinity (kcal/mol)
		Cefamandole	Cefapirin	Cefoxitin	Cefuroxime
SecA subunit PBP	Ab initio	−8.4	−7.9	−7.2	−8.2
OspE	2M4F	−7.1	−6.2	−7.3	−7.2

Abbreviations: SecA-PBP, subunit penicillin-binding protein; OspE, outer surface protein E.

Figure 2 Spatial arrangement of the in silico tested cephalosporins with secA translocase PBP of Borrelia burgdorferi: (A) cefamandole, (B) cefapirin, (C) cefoxitin, and (D) cefuroxime.

Note: The amino acid sequence of secA-PBP (B. burgdorferi B31) was retrieved from the Uniprot KB (Gene BB_0718) with a GenBank gene accession number of AE000783 (translation AAC67056.2.).
Abbreviation: PBP, penicillin-binding protein.

Table 4 Interaction of tested cephalosporins with Borrelia burgdorferi SecA-penicillin-binding protein (SecA-PBP)

Compound	Binding affinity (kcal/mol)	Types of interaction
		Strong hydrogen bonding	Van der Waals	Pi stacking	Alkyl
Cefamandole	−8.4	Tyr193, Ile676		Arg765, Tyr766
Cefapirin	−7.9	Lys374, Arg351, His358, Glu372, Thr229	Gly350, Glu338, Ile339, Leu348, Gly336, Glu362, Ala781, Gln359, Ser785	Glu230	Arg352, Ala370
Cefoxitin	−7.2	Arg138	Glu524, Ser489, Tyr134, Phe493, Val527, Thr515, Lys518	Trp142, Ala496, Ile523
Cefuroxime	−8.2	Ile523, Asn522, Tyr134, Glu524	Phe493, Arg138, Ala492, Thr515, Ala496, Lys518, Gly521