Genesis of Antibiotic Resistance XLVI: Inhibition of 3, 5, 6, trichloro‐2‐pyridinol (TCP) – Penicillin Binding Proteins (PBP) complex formation augment cross resistance to antibiotics (AR) and organophosphate insecticides in commensal symbiotic bacteria

Livestock industry utilizes approximately 70 to 80% of all antibiotics sold by volume in the U.S while the amount is projected to increase in countries like Brazil, Russia, India, China, and South Africa by 2030. The USDA‐APHIS‐VS a federal agency routinely monitor the livestock crossing (into and out of) the international borders as per the federal regulation under the supervision of veterinarian. Livestock are inspected for the signs and symptoms of zoonotic diseases in particular tuberculosis, cattle fever wobbling, and open abscess. Subsequent to the inspection, beef, non‐lactating cattle and horses dipped in the Co‐Ral® (EPA Reg: 11556‐98) (sulfate‐antidote) for the control of horn flies, lice, ticks, Screwworms, Scabies prior to the release to the owners. Based on the observation made during our field trips to United States Dept of Agri Inspection Station‐Eagle Pass, data analysis here we present a plausible mechanism(s) for Co‐Ral® induced eradication of the microbial pathogen(s). Co‐Ral® is an organophosphate insecticide that inhibits cholinesterase which catalyzes the hydrolysis of acetylcholine. Thus enabling the ectoparasites to accumulate acetylcholine lead to lack of coordination and neuromuscular block and subsequent paralysis. Development of insecticide resistance including carbamates, organophosphates, and pyrethroids by vectors (Mosquitos) has been reported all over the world. The bio transformed products formed during the course of biodegradation of organophosphate such as 3,5,6, trichloro‐2‐pyridinol (TCP) of chlorpyrifos and endosulfan sulfate of endosulfan were shown to cause toxicity similar to the of the parent compounds including symbiotic bacteria in GI tract of the vectors by binding to Penicillin Binding Proteins (PBP). However, symbiotic bacteria evolve antibiotic resistance by distorting the active site of the PBP lowering the acylation efficiency by β‐lactams (RJPBCS6 (64) Aug 2015) . Thus, blocking TCP‐PBP complex confers nullification of TCP induced bacterial toxicity while up regulate the antibiotic resistance genes repertoire (ARG) in commensal symbiotic bacteria (CSB) ( Path. Pub Health: 111 :( 6) 2017 page 292) in a time, dose and developmental stage specific pattern resulting antibiotic resistant CSB (arCSB). A direct correlation has been reported on the interdependency of symbiotic bacteria in the GI tract of Anopheles stephensi and its resistance to organophosphate insecticides (Abate ® (Temephos)). Based on the observation from the coculturing technique of symbiotic bacteria on the activity of the enzymes involved in An.stephensi , it was shown that presence of symbiotic bacteria resistant to antibiotics induced an increase in α‐esterase, Glutathione‐5‐Transferase (GST), Acetylcholine Esterase (AchE). Taken together, we suggest that exposure of CSB to xenobiotic(s) cause cross‐resistance to organophosphate insecticides and antibiotics exacerbating the probability of expedited Antibiotic Resistance Pandemic (ARP). Support or Funding Information Supported by Professional Development Funds by SWTJC to Subburaj Kannan This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .