Exposure to Sublethal Concentrations of Benzalkonium Chloride Induces Antimicrobial Resistance and Cellular Changes in Klebsiellae pneumoniae Clinical Isolates

Abstract

Benzalkonium chloride (BAC) is widely used as a disinfectant and preservative. This study investigated the effect on antimicrobial susceptibility and the cellular changes that occurred after exposure of Klebsiella pneumoniae clinical isolates to sublethal concentrations of BAC. Minimum inhibitory concentration and minimum bactericidal concentration of BAC were determined for the collected 50 K. pneumoniae clinical isolates by broth microdilution method, and the tested isolates were adapted to increasing sublethal concentrations of BAC. The effect of adaptation on MICs of the tested 16 antimicrobial agents, the cell ultrastructure, efflux, and membrane depolarization of the tested isolates were examined. Interestingly, most K. pneumoniae isolates that adapted to BAC showed increased antimicrobial resistance, various morphological and structural changes, increased membrane depolarization, and enhanced efflux activity. The findings of this study suggest that the extensive use of BAC at sublethal concentrations could contribute to the emergence of antibiotic resistance in K. pneumoniae clinical isolates that might complicate the therapy of infections caused by this pathogen. In conclusion, the hazard associated with the prolonged exposure to sublethal concentrations of BAC represents a public health risk and therefore it should be a focus in both hospital and community sanitation practices.

Potential impact of biocide adaptation on selection of antibiotic resistance in bacterial isolates

“…There is an immediate indication of the bacterial fitness costs in the laboratory, in terms of decreased size of colonies or other growth properties [53], or the cost may be only observed in the communities where there is a competition within and between different microbial species. However, co-selection is not often costly and prolonged exposure to biocides may select compensatory adaptations which could restore the bacterial fitness [17,54]. Moreover, certain resistance adaptations, such as enhancement of biofilm formation, may improve the bacterial survival in other environments [55].…”

Biocide-Induced Emergence of Antibiotic Resistance in Escherichia coli

“…ALE studies have been conducted in Escherichia coli (E. coli) for a range of stressful conditions, which included acid (Johnson et al, 2014;Harden et al, 2015;Zorraquino et al, 2017), osmotic (Zorraquino et al, 2017), antibiotics (Lázár et al, 2014;Oz et al, 2014), and biocides (Braoudaki and Hilton, 2004;Bore et al, 2007;Wand et al, 2017;Abdelaziz et al, 2019;Verspecht et al, 2019). The adaptation to common disinfectants and antiseptics, and the emergence of cross-resistance to chemicals such as antibiotics, was demonstrated for bacteria exposed to biocides such as benzalkonium chloride (Braoudaki and Hilton, 2004;Bore et al, 2007;Abdelaziz et al, 2019) and chlorhexidine (Braoudaki and Hilton, 2004;Wand et al, 2017;Verspecht et al, 2019) and reviewed elsewhere (Kampf, 2018). In the field, decreased susceptibility to biocides in association with antibiotic resistance was observed through the co-resistance phenomena (Cho et al, 2013;Gomaa et al, 2017).…”

Extreme genome selection towards complete antimicrobial resistance in a nosocomial strain ofStenotrophomonas maltophiliacomplex

“…Hence, the effectiveness of cleanliness is always under question as the hospital settings are shown to be rapidly contaminated by deadly pathogens with multidrug resistant organisms like: Acinetobacter spp., Klebsiella pneumonia etc. (36, 37). These nosocomial pathogens have been shown to persist in the hospital environment from some days to even months (38).…”