Campestre Cristina, De Luca Viviana, Carradori Simone, Grande Rossella, Carginale Vincenzo, Scaloni Andrea, Supuran Claudiu T, Capasso Clemente
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Department of Biology, Agriculture and Food Sciences, National Research Council (CNR), Institute of Biosciences and Bioresources, Naples, Italy.
Front Microbiol. 2021 Mar 19;12:629163. doi: 10.3389/fmicb.2021.629163. eCollection 2021.
Our understanding of the function of bacterial carbonic anhydrases (CAs, EC 4.2.1.1) has increased significantly in the last years. CAs are metalloenzymes able to modulate CO, HCO and H concentration through their crucial role in catalysis of reversible CO hydration (CO + HO ⇄ HCO + H). In all living organisms, CA activity is linked to physiological processes, such as those related to the transport and supply of CO or HCO , pH homeostasis, secretion of electrolytes, biosynthetic processes and photosynthesis. These important processes cannot be ensured by the very low rate of the non-catalyzed reaction of CO hydration. It has been recently shown that CAs are important biomolecules for many bacteria involved in human infections, such as , , , , and . In these species, CA activity promotes microorganism growth and adaptation in the host, or modulates bacterial toxin production and virulence. In this review, recent literature in this research field and some of the above-mentioned issues are discussed, namely: () the implication of CAs from bacterial pathogens in determining the microorganism growth and virulence; () the druggability of these enzymes using classical CA inhibitors (CAIs) of the sulfonamide-type as examples; () the role played by CAs in the acid tolerance/adaptation of the microbe within the human abdomen; () the role of CAs played in the outer membrane vesicles spawned by in its planktonic and biofilm phenotypes; () the possibility of using CAIs in combination with probiotic strains as a novel anti-ulcer treatment approach. The latter approach may represent an innovative and successful strategy to fight gastric infections in the era of increasing resistance of pathogenic bacteria to classical antibiotics.
近年来，我们对细菌碳酸酐酶（CAs，EC 4.2.1.1）功能的理解有了显著提高。碳酸酐酶是一种金属酶，通过在可逆的CO水合作用（CO + H₂O ⇄ HCO₃⁻ + H⁺）催化中的关键作用，能够调节CO₂、HCO₃⁻和H⁺的浓度。在所有生物中，碳酸酐酶的活性都与生理过程相关，比如与CO₂或HCO₃⁻的运输和供应、pH稳态、电解质分泌、生物合成过程以及光合作用有关的生理过程。CO₂水合的非催化反应速率极低，无法确保这些重要过程的进行。最近的研究表明，碳酸酐酶对于许多引起人类感染的细菌而言是重要的生物分子，例如[具体细菌名称1]、[具体细菌名称2]、[具体细菌名称3]、[具体细菌名称4]和[具体细菌名称5]。在这些物种中，碳酸酐酶的活性促进微生物在宿主体内的生长和适应，或调节细菌毒素的产生和毒力。在本综述中，将讨论该研究领域的最新文献以及上述一些问题，具体如下：（1）细菌病原体中的碳酸酐酶在决定微生物生长和毒力方面的作用；（2）以磺酰胺类经典碳酸酐酶抑制剂（CAIs）为例，这些酶的可药用性；（3）碳酸酐酶在微生物于人体腹部的耐酸性/适应性方面所起的作用；（4）碳酸酐酶在[细菌名称]产生的外膜囊泡的浮游和生物膜表型中所起的作用；（5）将碳酸酐酶抑制剂与益生菌菌株联合使用作为一种新型抗溃疡治疗方法的可能性。在病原菌对经典抗生素耐药性不断增加的时代，后一种方法可能代表了一种创新且成功的对抗胃部感染的策略。
