1. Academic Validation
  2. Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31

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

  • Sci Rep. 2020 Mar 2;10(1):3798. doi: 10.1038/s41598-020-59600-4.
Venkata Raveendra Pothineni 1 Hari-Hara S K Potula 1 Aditya Ambati 2 Venkata Vamsee Aditya Mallajosyula 3 Brindha Sridharan 4 Mohammed Inayathullah 1 Mohamed Sohail Ahmed 1 Jayakumar Rajadas 5 6 7
Affiliations

Affiliations

  • 1 Biomaterials and Advanced Drug Delivery, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, California, 94304, USA.
  • 2 Center for sleep sciences and medicine, Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Palo Alto, California, 94304, USA.
  • 3 Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • 4 Department of Plant Biology and Biotechnology, Loyola College, Chennai, 600 034, Tamil Nadu, India.
  • 5 Biomaterials and Advanced Drug Delivery, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, California, 94304, USA. jayraja@stanford.edu.
  • 6 Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine, Palo Alto, California, 94304, USA. jayraja@stanford.edu.
  • 7 Bioengineering and Therapeutic Sciences, UCSF School of Pharmacy, University of California, San Francisco, CA, 94158, USA. jayraja@stanford.edu.
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.

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