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.

Plasmonic Au@Ag@mSiO2 Nanorattles for In Situ Imaging of Bacterial Metabolism by Surface-Enhanced Raman Scattering Spectroscopy

“…In this context, bacteria can metabolically adapt to sublethal environmental acid stress (pH 5.5–4.5) by inducing an adaptive tolerance response, 58 which has been linked to antibiotic resistance. 59 Moreover, acidic pH sensing is required for virulence. 60 Also, the detection of pH changes as a result of microbial metabolism during growth is a means to assess the bacterial response to antibiotics.…”

“…To achieve pH homeostasis, bacterial cells possess regulatory networks that govern the expression of distinct sets of genes under acid and alkaline conditions. In this context, bacteria can metabolically adapt to sublethal environmental acid stress (pH 5.5–4.5) by inducing an adaptive tolerance response, which has been linked to antibiotic resistance . Moreover, acidic pH sensing is required for virulence .…”

Isolation, characterization, and antimicrobial susceptibility pattern of Escherichia coli O157:H7 from foods of bovine origin in Mekelle, Tigray, Ethiopia

“…Most of these microbes have zoonotic importance resulting in a signi cant impact on both public health and economic sectors [4]. Moreover, the emergence of multidrug-resistant pathogens presents a global challenge for treating and preventing disease spread through zoonotic transmission [5].…”

Bacterial Stress Responses as Potential Targets in Overcoming Antibiotic Resistance

“…Nutrient starvation can also induce biofilm formation, which leads to enhanced antibiotic resistance and is involved in chronic infections [ 10 , 11 ]. Other growth-limiting stresses, such as low pH and high temperature, induce several molecular rearrangements at the cellular metabolic level that are involved in the regulation of bacterial responses to antibiotics [ 12 ]. Bacterial stress responses not only encourage adaptation but also promote the virulence responsible for bacterial survival in stressful environments [ 13 ].…”