Antibiotics

PATHOGENSIntroductionThe Challenge of Treating Dormant InfectionsDiscovery Strategies to Prevent or Kill Dormant BacteriaWhy Targeting the Membrane Could Be a Suitable StrategyTarget Essentiality and SelectivityMultiple Modes of ActionsTherapeutic Use of Membrane-Damaging Agents against BiofilmsNew Approaches to Identifying Compounds That Kill Dormant BacteriaChallenges for Biofilm Control with Membrane-Active AgentsPotential for Membrane-Damaging Agents in TB DiseaseApplication to Treatment for Clostridium difficile InfectionIs Inhibition of Fatty Acid/Phospholipid Biosynthesis Also an Approach?Concluding RemarksBACTERIAL MEMBRANE, A KEY FOR CONTROLLING DRUG INFLUX AND EFFLUXIntroductionThe Mechanical BarrierCircumventing the Bacterial Membrane BarrierConclusionINTERFERENCE WITH BACTERIAL CELL-TO-CELL CHEMICAL SIGNALING IN DEVELOPMENT OF NEW ANTI-INFECTIVESIntroductionTwo-Component Systems (TCSs) as Potential Anti-Infective TargetsWalK/WalR and MtrB/MtrA: Case Studies of Essential TCSs as Drug TargetsTargeting Nonessential TCSNon-TCSs Targeting Biofilm Formation and Quorum Sensing in Pseudomonas spp.ConclusionsRECENT DEVELOPMENTS IN INHIBITORS OF BACTERIAL TYPE IIA TOPOISOMERASESIntroductionDNA-Gate InhibitorsATPase-Domain InhibitorsSimocyclinones, Gyramides, and Other Miscellaneous InhibitorsConclusions and PerspectivesANTIBIOTICS TARGETING BACTERIAL RNA POLYMERASEIntroductionAntibiotics Blocking Nascent RNA ExtensionAntibiotics Targeting RNAP Active CenterAntibiotics Blocking Promoter Complex FormationInhibitors Hindering Sigma-Core InteractionsInhibitors with Unknown Mechanisms and Binding SitesConclusions and PerspectivesINHIBITORS TARGETING RIBOSWITCHES AND RIBOZYMESIntroductionRiboswitches as Antibacterial Drug TargetsRibozymes as Antibacterial Drug TargetsConcluding Remarks and Future PerspectivesTARGETING RIBONUCLEASE PIntroductionTargeting RNase P with Antisense StrategiesAminoglycosidesPeptidyltransferase InhibitorsSubstrate Masking by Synthetic InhibitorsPeculiar Behavior of Macrolides on Bacterial RNase PAntipsoriatic CompoundsConclusions and Future PerspectivesINVOLVEMENT OF RIBOSOME BIOGENESIS IN ANTIBIOTIC FUNCTION, ACQUIRED RESISTANCE, AND FUTURE OPPORTUNITIES IN DRUG DISCOVERYIntroductionRibosome BiogenesisMethyltransferasesMethyltransferase Integration into the Ribosome Biogenesis PathwayRibosome Biogenesis Factors, Virulence, and Vaccine DevelopmentAMINOACYL-Trna Synthetase InhibitorsIntroductionEnzymatic Mechanism of Action of aaRSaaRS InhibitorsConsiderations for the Development of aaRS InhibitorsConclusionsANTIBIOTICS TARGETING TRANSLATION INITIATION IN PROKARYOTESIntroductionMechanism of Translation InitiationInhibitors of Folate MetabolismMethionyl-tRNA FormyltransferaseInhibitors of Peptide DeformylaseInhibitors of Translation Initiation Factor IF2ppGpp Analogs as Potential Translation Initiation InhibitorsTranslation Initiation Inhibitors Targeting the P-SiteINHIBITORS OF BACTERIAL ELONGATION FACTOR EF-TuIntroductionEnacyloxinsKirromycinPulvomycinGE2270AAMINOGLYCOSIDE ANTIBIOTICS: STRUCTURAL DECODING OF INHIBITORS TARGETING THE RIBOSOMAL DECODING A SITEIntroductionChemical Structures of AminoglycosidesSecondary Structures of the Target A SitesOverview of the Molecular Recognition of Aminoglycosides by the Bacterial A SiteRole of Ring I: Specific Recognition of the Binding PocketRole of Ring II (2-DOS Ring): Locking the A-Site Switch in the "On" StateDual Roles of Extra Rings: Improving the Binding Affinity and Eluding Defense MechanismsBinding of Semisynthetic Aminoglycosides to the Bacterial A SitesBinding of Aminoglycosides to the Antibiotic-Resistant Bacterial Mutant and Protozoal Cytoplasmic A SitesBinding of Aminoglycosides to the Human A SitesOther Aminoglycosides Targeting the A Site but with Different Modes of ActionAminoglycosides that Do Not Target the A SiteNonaminoglycoside Antibiotic Targeting the A SiteConclusionsPEPTIDYLTRANSFERASE INHIBITORS OF THE BACTERIAL RIBOSOMEPeptide Bond Formation and Its Inhibition by AntibioticsPuromycin Mimics the CCA-End of tRNAsChloramphenicols Inhibit A-tRNA Binding in an Amino-Acid-Specific MannerThe Oxazolidinones Bind at the A-Site of the PTCLincosamide Action at the A-Site of the PTCBlasticidin S Mimics the CCA-End of the P-tRNA at the PTCSparsomycin Prevents A-Site and Stimulates P-Site tRNA BindingPleuromutilins Overlap A- and P-Sites at the PTCThe Synergeistic Action of Streptogramins at the PTCFuture PerspectivesANTIBIOTICS INHIBITING THE TRANSLOCATION STEP OF PROTEIN ELONGATION ON THE RIBOSOMEIntroductionTranslocation: OverviewAntibiotics Inhibiting TranslocationAntibiotics Inhibiting Translocation in EukaryotesAntibiotics Inhibiting Ribosome Recycling in BacteriaPerspectiveANTIBIOTICS AT THE RIBOSOMAL EXIT TUNNEL - SELECTRED STRUCTURAL ASPECTSIntroductionThe Multifunctional TunnelA Binding Pocket within the Multifunctional TunnelRemotely ResistanceResistance WarfareSynergismPathogen and "Patiens" ModelsConclusion and Future ConsiderationsTARGETING HSP70 TO FIGHT CANCER AND BAG BUGS: ONE AND THE SAME BATTLE?A Novel Target: The Bacterial Chaperone HSP70An In vivo Screening for Compounds Targeting DnaKDrugging HSP70Cooperation between the Bacterial Molecular Chaperones DnaK and HtpGDrugging HSP90Index