Bacteria are continually challenged with variety of synthetic chemicals/xenobiotics in their immediate surroundings, including pesticides. Chlorpyrifos (CP) is one of the most commonly used organophosphate pesticides in the world. The non-environmental strain of Escherichia coli, BL21 (DE3) displayed high tolerance to chlorpyrifos but with no/negligible degradation. The intrinsic resistance mechanisms that aid the organism in its high tolerance were probed. Efflux pumps being ubiquitous in

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... e and capable of conferring resistance against wide variety of xenobiotics were probes and was found to be over-expressed in CP stress. Also, an efflux pump inhibitor PAβN increased the susceptibility of E. coli to the pesticide due to the intracellular accumulation of CP. The tripartite efflux pump EmrAB-TolC with increased expression in both transcript and protein on CP exposure, might play a major role in CP tolerance. The transcriptional regulators involved in multidrug resistance along with transporters belonging to all the major families conferring antimicrobial resistance were up-regulated. Also up-regulated were the genes involved in phopshonate metabolism, and all the genes in the copper or silver export system. The common resistance mechanisms i.e, activation of efflux pumps between CP, antibacterial metals and antibiotics resistance could result in cross-resistance, ultimately increasing the prevalence of multidrug resistant strains, making infections hard to treat.