Targets and assays for discovering novel antibacterial agents.
The increasing frequency of nosocomial infections due to multi-resistant pathogens exerts a significant toll and calls for novel and better antibiotics. Different approaches can be used in the search for novel antibiotics acting on drug-resistant bacterial pathogens. We present some considerations on valid bacterial targets to be used for searching new antibiotics, and how the information from bacterial genome sequences can assist in choosing the appropriate targets. Other factors to be considered in target selection are the chemical diversity available for screening and its uniqueness. We will conclude discussing our strategy for searching novel antibacterials. This is based on a large collection of microbial extracts as a source of chemical diversity and on the use of specific targets essential for the viability of bacterial pathogens. Two assay strategies have been implemented: a pathway-based assay, where a series of essential bacterial targets is screened in a single assay; and a binding assay, where many targets can be screened individually in the same format.
Donadio
Stefano
S
Biosearch Italia, via R. Lepetit 34, 21040 Gerenzano(VA), Italy. sdonadio@biosearch.it
Carrano
Lucia
L
Brandi
Letizia
L
Serina
Stefania
S
Soffientini
Adolfo
A
Raimondi
Elena
E
Montanini
Nicoletta
N
Sosio
Margherita
M
Gualerzi
Claudio O
CO
D000900:Anti-Bacterial Agents / Q000145:classification / Q000302:isolation & purification* / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy*; D001681:Biological Assay / Q000379:methods; D015415:Biomarkers; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D025141:Drug Resistance, Fungal; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods; D016680:Genome, Bacterial; D016681:Genome, Fungal; D015698:Genomic Library; D006801:Humans; D040081:Protein Array Analysis / Q000379:methods*
D000900:Anti-Bacterial Agents; D015415:Biomarkers