Abstract:
: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.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Campanini B,Pieroni M,Raboni S,Bettati S,Benoni R,Pecchini C,Costantino G,Mozzarelli Adoi
10.2174/0929867321666141112122553subject
Has Abstractpub_date
2015-01-01 00:00:00pages
187-213issue
2eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-63369journal_volume
22pub_type
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