Current Understanding of Potential Linkages between Biocide Tolerance and Antibiotic Cross-Resistance

Abstract

Antimicrobials (e.g., antibiotics and biocides) are invaluable chemicals used to control microbes in numerous contexts. Because of the simultaneous use of antibiotics and biocides, questions have arisen as to whether environments commonly treated with biocides (e.g., hospitals, food processing, wastewater, agriculture, etc.) could act as a reservoir for the development of antibiotic cross-resistance. Theoretically, cross-resistance could occur if the mechanism of bacterial tolerance to biocides also resulted in antibiotic resistance. On the other hand, biocides would likely present a higher evolutionary barrier to the development of resistance given the different modes of action between biocides and antibiotics and the broad-based physicochemical effects associated with most biocides. Published studies have shown that the induction of biocide tolerance in a laboratory can result in cross-resistance to some antibiotics, most commonly hypothesized to be due to efflux pump upregulation. However, testing of environmental isolates for biocide tolerance and antibiotic cross-resistance has yielded conflicting results, potentially due to the lack of standardized testing. In this review, we aim to describe the state of the science on the potential linkage between biocide tolerance and antibiotic cross-resistance. Questions still remain about whether the directed evolution of biocide tolerance and the associated antibiotic cross-resistance in a laboratory are or are not representative of real-world settings. Thus, research should continue to generate informative data to guide policies and preserve these tools’ utility and availability.

Effects of Three Antibiotics on Nitrogen-Cycling Bacteria in Sediment of Aquaculture Water

“…These authors suggested that after the function of AOB was inhibited, AOA with the same ecological function was further strengthened, thereby supplementing the functional deficiency of AOB (functional redundancy between AOA and AOB). There were significant differences in the effects of the three antibiotics on AOA amoA and AOB amoA, indicating that ammonia-oxidizing microorganisms have different sensitivities to various antibiotics, which may be due to the degree of tolerance and adaptation of microorganisms to antibiotics [42]. OTC had the strongest inhibitory effect on nosZ gene abundance, which was consistent with the findings of previous studies.…”

A Critical Review of AMR Risks Arising as a Consequence of Using Biocides and Certain Metals in Food Animal Production

“…Biocidal substances act in different ways and sometimes several biocides are combined within a single product to increase the overall antimicrobial efficacy [8]. The mechanisms of action and tolerance to a wide range of biocides on bacteria have been reviewed and described widely in the literature [5,[9][10][11]. Biocides generally act on multiple targets unless present at sub-inhibitory or low concentration [8], although exact mechanisms of action are not fully understood, and are also organism specific.…”

“…They also have antimicrobial properties and may be used for this purpose in food animal production. The antimicrobial modes/mechanisms of action of metals on bacteria have been reviewed and described in the literature [5,18,19]. As with biocides, the exact mechanisms of action still remain unclear and are also organism specific, but reported actions include effects on the cell wall or membrane; interactions with DNA; binding or inhibition of enzymes and membrane proteins.…”

“…Co-selection mechanisms for biocides and/or metals and clinically as well as veterinaryrelevant antibiotics are described widely in the literature [3,5,12,[30][31][32], amongst others. There are two main types of related resistance/tolerance co-selection mechanisms:…”

“…However, clinical breakpoints are not available for all antimicrobial agents/bacteria combinations. This is particularly the case for agents such as biocides and metals, where no internationally accepted breakpoints exist to define resistance [3][4][5]. While MICs can be determined for biocides and metals, since they are used differently to antibiotics (as discussed in a further section) relying on MIC measurements can be misleading.…”