Sheikh Salma Waheed, Ali Ahmad, Ahsan Asma, Shakoor Sidra, Shang Fei, Xue Ting
School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.
School of Agronomy, Anhui Agricultural University, Hefei 230036, China.
Antibiotics (Basel). 2021 May 2;10(5):522. doi: 10.3390/antibiotics10050522.
The emergence of multidrug-resistant pathogens presents a global challenge for treating and preventing disease spread through zoonotic transmission. The water and foodborne Enterohaemorrhagic (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.
多重耐药病原体的出现给通过人畜共患病传播来治疗和预防疾病传播带来了全球性挑战。水源性和食源性肠出血性大肠杆菌（EHEC）能够引发肠道和全身性疾病。这些菌株出现的根本原因是它们对环境应激源，尤其是酸性pH的代谢适应。人们期望通过酸处理来杀死病原体，但EHEC所采用的保护机制会交叉保护其抵御抗菌肽，从而为其生存和致病创造机会。在本综述中，我们讨论了耐酸性与抗生素耐药性之间的相关性，强调了识别新型靶点以用于潜在的抗菌治疗药物生产。我们还总结了适应酸性环境的EHEC所使用的分子机制，例如介导结构修饰、竞争性抑制和促进对抗菌化合物交叉保护的外排激活的双组分反应系统。超越描述性研究，本综述强调低pH应激是对抗菌剂交叉保护发展过程中一个新出现的因素。我们还描述了创新治疗方法的潜在基因靶点，以克服医疗保健和工业中多重耐药疾病的风险。
