Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Impact of Environmental Sub-Inhibitory Concentrations of Antibiotics, Heavy Metals, and Biocides on the Emergence of Tolerance and Effects on the Mutant Selection Window in E. coli

Version 1 : Received: 16 July 2023 / Approved: 17 July 2023 / Online: 18 July 2023 (05:36:57 CEST)

A peer-reviewed article of this Preprint also exists.

Chukwu, K.B.; Abafe, O.A.; Amoako, D.G.; Ismail, A.; Essack, S.Y.; Abia, A.L.K. Impact of Environmental Sub-Inhibitory Concentrations of Antibiotics, Heavy Metals, and Biocides on the Emergence of Tolerance and Effects on the Mutant Selection Window in E. coli. Microorganisms 2023, 11, 2265. Chukwu, K.B.; Abafe, O.A.; Amoako, D.G.; Ismail, A.; Essack, S.Y.; Abia, A.L.K. Impact of Environmental Sub-Inhibitory Concentrations of Antibiotics, Heavy Metals, and Biocides on the Emergence of Tolerance and Effects on the Mutant Selection Window in E. coli. Microorganisms 2023, 11, 2265.

Abstract

Bacteria’s ability to withstand the detrimental effects of antimicrobials may take the form of resistance or tolerance with the minimum inhibitory concentration (MIC), the mutant prevention concentration (MPC), and the mutant selection window as salient concepts. Isolates exposed for 30 days to different concentrations of selected antibiotics, biocides, and heavy metals, singly and in combination, were additionally exposed to very high (15 × MIC) concentrations of ampicillin., and their tolerance was calculated the time to kill 99.9% of the isolate population (MDK99.9). These values were increased by 30 to 50% in test isolates compared to the untreated control. BAC 10-exposed isolates had the highest tolerance increase, and the tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes using diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the amplification of persister cells during the 30-day exposure. These findings indicate that bacterial exposure to sub-inhibitory concentrations of environmental chemical stressors may not always result in the development of antimicrobial resistance but could initiate this process by selecting for persisters that could evolve into resistant isolates.

Keywords

environmental stressors; pharmaceuticals; antibiotic resistance; selection pressure; public health; tolerant bacteria; environmental pollution; mutation; whole genome sequencing; single nucleotide polymorphisms

Subject

Public Health and Healthcare, Public, Environmental and Occupational Health

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