Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31

Abstract

Lyme disease is one of most common vector-borne diseases, reporting more than 300,000 cases annually in the United States. treating Lyme disease during its initial stages with traditional tetracycline antibiotics is effective. However, 10-20% of patients treated with antibiotic therapy still shows prolonged symptoms of fatigue, musculoskeletal pain, and perceived cognitive impairment. When these symptoms persists for more than 6 months to years after completing conventional antibiotics treatment are called post-treatment Lyme disease syndrome (ptLDS). though the exact reason for the prolongation of post treatment symptoms are not known, the growing evidence from recent studies suggests it might be due to the existence of drug-tolerant persisters. In order to identify effective drug molecules that kill drug-tolerant borrelia we have tested two antibiotics, azlocillin and cefotaxime that were identified by us earlier. The in vitro efficacy studies of azlocillin and cefotaxime on drug-tolerant persisters were done by semisolid plating method. the results obtained were compared with one of the currently prescribed antibiotic doxycycline. We found that azlocillin completely kills late log phase and 7-10 days old stationary phase B. burgdorferi. our results also demonstrate that azlocillin and cefotaxime can effectively kill in vitro doxycycline-tolerant B. burgdorferi. Moreover, the combination drug treatment of azlocillin and cefotaxime effectively killed doxycycline-tolerant B. burgdorferi. furthermore, when tested in vivo, azlocillin has shown good efficacy against B. burgdorferi in mice model. These seminal findings strongly suggests that azlocillin can be effective in treating B. burgdorferi sensu stricto JLB31 infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy. Lyme disease is a major vector-borne disease in the United States caused by Borrelia burgdorferi sensu lato which affects more than 300,000 people annually 1-3. Lyme disease affects various organs such as brain, skin, heart, joints, and nervous systems 4-6. The symptoms of Lyme disease are erythema migrans, fatigue, fever, headache, chills, muscle and joint pain 7,8. Current antibiotic treatment for Lyme disease is effective during early stages of disease and cures the infection in most patients 9. However, 10-20% of patients undergone antibiotic treatment still experience symptoms like pain, fatigue, arthralgia, and cognitive problems. If these symptoms prolong more than 6 months after treatment, it is referred to as Post-treatment Lyme Disease Syndrome (PTLDS) 9-12. Though the exact root cause for PTLDS is not known, research evidences suggests it might be presence of persister forms of B. burgdorferi or due to impaired immunological response 10,13,14. Many research studies has shown that B.

Computational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2

“…Azlocillin, a wide-spectrum acylated form of ampicillin with antibacterial activity, has been recently proposed as a potential drug candidate for Lyme disease (targeting drugtolerant Borrelia burgdorferi). Besides its efficacy, the safety of azlocillin was one of the main criteria for selecting this drug (Pothineni et al, 2020). In terms of drug repositioning, note that azlocillin has also been investigated as a potential new therapeutic agent for prostate cancer (Turanli et al, 2019).…”

Antibiotic Susceptibility of Bartonella Grown in Different Culture Conditions

“…The lowest MIC of ampicillin that inhibited the growth of all the 11 isolates was <0.016 mg/L, which is consistent with our MIC data. Azlocillin is a β-lactam antibiotic that has recently garnered interest because it showed good efficacy against Borrelia burgdorferi both in vitro and in a mouse model [29]. Azlocillin was the most potent drug among all the antibiotics that were used in this study.…”

Ex Vivo Murine Skin Model for B. burgdorferi Biofilm

“…Antibiotic and antimicrobial testing for various morphological forms of B. burgdorferi , including spirochetes, cyst/round body, and biofilm forms, is primarily conducted in vitro with novel as well as certain combinations of previously discovered antimicrobial agents [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Those studies provided strong evidence that the most antibiotic resistant form of B. burgdorferi is the biofilm [ 38 , 73 , 75 , 76 ], which agrees with the data for biofilm resistance of other pathogenic species [ 43 , 44 , 45 , 46 , 47 ].…”