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.