Insights into Emergence of Antibiotic Resistance in Acid-Adapted Enterohaemorrhagic Escherichia coli

Abstract

The emergence of multidrug-resistant pathogens presents a global challenge for treating and preventing disease spread through zoonotic transmission. The water and foodborne Enterohaemorrhagic Escherichia coli (EHEC) are capable of causing intestinal and systemic diseases. The root cause of the emergence of these strains is their metabolic adaptation to environmental stressors, especially acidic pH. Acid treatment is desired to kill pathogens, but the protective mechanisms employed by EHECs cross-protect against antimicrobial peptides and thus facilitate opportunities for survival and pathogenesis. In this review, we have discussed the correlation between acid tolerance and antibiotic resistance, highlighting the identification of novel targets for potential production of antimicrobial therapeutics. We have also summarized the molecular mechanisms used by acid-adapted EHECs, such as the two-component response systems mediating structural modifications, competitive inhibition, and efflux activation that facilitate cross-protection against antimicrobial compounds. Moving beyond the descriptive studies, this review highlights low pH stress as an emerging player in the development of cross-protection against antimicrobial agents. We have also described potential gene targets for innovative therapeutic approaches to overcome the risk of multidrug-resistant diseases in healthcare and industry.

Keywords: acid tolerance; cross-protection; enterohaemorrhagic Escherichia coli; foodborne infections; multidrug resistance; two-component signaling system.

Figure 1

Representation of the oxidative, glutamate-dependent, arginine-dependent, and lysine-dependent acid resistance systems in Escherichia coli. All abbreviations are listed at the end of the manuscript.

Figure 2

Schematic representation of acid stress regulation by different two-component signal transduction systems, acid-resistance networks, and their interconnecting assemblies. All abbreviations are defined at the end of the manuscript.

Figure 3

Schematic representation of the acid-induced activation of a specific set of genes by two-component systems leading to LPS modification, efflux pump activation, enhanced survival, and antibiotic resistance in EHECs. All abbreviations are defined at the end of the manuscript.