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. 2023 Sep 9;11(9):2265.
doi: 10.3390/microorganisms11092265.

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

Kelechi B Chukwu  1 , Ovokeroye A Abafe  1   2   3 , Daniel G Amoako  1   4 , Arshad Ismail  5   6 , Sabiha Y Essack  1 , Akebe L K Abia  1   7
Affiliations

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

Kelechi B Chukwu et al. Microorganisms. .

Abstract

Bacteria's ability to withstand the detrimental effects of antimicrobials could occur as resistance or tolerance with the minimum inhibitory concentration, the mutant prevention concentration, and the mutant selection window as salient concepts. Thus, this study assessed the impact of exposure to extremely high doses of ampicillin on the level of persistence and tolerance development in isolates previously exposed to different concentrations of selected antibiotics, biocides, and heavy metals. These isolates were previously exposed to oxytetracycline (OXYTET), amoxicillin (AMX), copper (Cu), zinc (Zn), benzalkonium chloride (BAC) 10, dimethylammonium chloride (DADMAC) 12 and a combination of all the individual pollutants (ALL). The isolates were exposed to very high concentrations (25 × MIC) of ampicillin, and their tolerance was calculated as the time required to kill 99.9% of the bacterial population (MDK99.9). The MDK99.9 increased by 30 to 50% in test isolates (DADMAC, OXYTET, Zinc = 28 h; BAC, Copper = 30 h; amoxycillin, ALL = 26 h) compared to the untreated control. BAC-exposed isolates decreased from 2.5 × 108 CFU/mL to 2.5 × 104 CFU/mL on the second day, displaying the highest tolerance increase. The tolerance appeared to originate from two sources, i.e., stochastic persistence and genetic-induced persistence, involving multiple genes with diverse mechanisms. The mutant selection window of the isolates to ampicillin, amoxicillin, and oxytetracycline also slightly increased compared to the control, indicating the selective survival 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 persisters that could evolve into resistant isolates.

Keywords: antibiotic resistance; environmental pollution; environmental stressors; mutation; public health; selection pressure; single nucleotide polymorphisms; tolerant bacteria.

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Conflict of interest statement

Sabiha Y. Essack is the Global Respiratory Infection Partnership and a member of the Global Hygiene Council, both sponsored by unconditional educational grants from Reckitt, UK. All other authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The minimum duration for killing 99.99% (MDK99.99) of bacterial cells in the population for BAC (benzalkonium chloride)- and DADMAC (dimethylammonium chloride)-exposed isolates compared to the control.
Figure 2
Figure 2
The minimum time required to kill 99.99% (MDK99.99) of the AMX (amoxycillin)- and OXYTET (oxytetracycline)-exposed isolates compared to the control.
Figure 3
Figure 3
The minimum time required to kill 99.99% (MDK99.99) of the zinc- and copper-exposed isolates compared to the control.
Figure 4
Figure 4
The minimum time required to kill 99.99% (MDK99.99) of the ALL (combined chemicals)-exposed isolates compared to the control.
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