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.
Keywords: Antibiotic resistance, antibiotics, cysteine biosynthesis, Mycobacterium tuberculosis, O-acetylserine sulfhydrylase,
reductive sulfate assimilation pathway, sulfur metabolism.
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