细菌性病原体的硫同化通路抑制剂作为抗生素疗法的增强剂

Title:Inhibitors of the Sulfur Assimilation Pathway in Bacterial Pathogens as Enhancers of Antibiotic Therapy

Volume: 22 Issue: 2

Author(s): Barbara Campanini, Marco Pieroni, Samanta Raboni, Stefano Bettati, Roberto Benoni, Chiara Pecchini, Gabriele Costantino and Andrea Mozzarelli

Affiliation:

关键词: 抗生素耐药性，抗生素，半胱氨酸生物合成，结核杆菌，乙酰丝氨酸巰解酶，还原性的硫同化通路，硫新陈代谢。

摘要: The rising emergence of antibiotic resistance urges the search for new strategies to defeat microorganisms that lead to persistent infections of the host. Tolerant to antibiotics, slowly replicating bacteria often cause latent and persistent infections that are the most challenging for pharmacological treatment. Persistence inside the host requires an extensive re-programming of the pathogen metabolic functions, due to the extremely hostile environment they face. Therefore, targeting key metabolic functions could result in better antibiotic treatments, shortened latency periods, and increased susceptibility to traditional antibiotics. Bacteria, differently from mammals, assimilate inorganic sulfur into cysteine, the precursor of a number of key metabolites including reducing agents, cofactors and membrane components. Inhibition of cysteine biosynthesis was proven to interfere heavily with the ability of pathogens to fight oxidative stress, to infect the host and to establish long-term infections. This review has the purpose of i) briefly summarizing the key structural and functional properties of transporters and enzymes involved in sulfur assimilation, ii) presenting biological evidence that supports the exploitation of this pathway for the identification of potential targets and, iii) highlighting intense efforts and advancements in the search of promising candidates for the development of novel compounds that enhance antibiotics therapy.

Cite this article as:

Barbara Campanini , Marco Pieroni , Samanta Raboni , Stefano Bettati , Roberto Benoni , Chiara Pecchini , Gabriele Costantino and Andrea Mozzarelli , Inhibitors of the Sulfur Assimilation Pathway in Bacterial Pathogens as Enhancers of Antibiotic Therapy, Current Medicinal Chemistry 2015; 22 (2) . https://dx.doi.org/10.2174/0929867321666141112122553