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Antimicrobials pp 327–360Cite as

Strategies to Discover Novel Antimicrobials to Cope with Emerging Medical Needs

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Abstract

The antibacterial screening strategies developed since the 1990s have seen an important evolution from the low throughput early phenotypic assays used to identify compounds targeting specific pathogens to target-based whole cell assays and structured-based design derived from in silico screening. Whereas empirical and target-based methods have been widely applied to screen for antibacterial agents, novel approaches such as structure-based drug design have proved to be a successful approach in other therapeutic areas, but they have not yet been widely applied to the development of antibacterial drugs. The objective of all these approaches has been the discovery of chemically novel leads that inhibit new molecular targets, or inhibit established targets by mechanisms distinct from those exploited by existing drugs. The focus of this chapter is to review a selection of different drug discovery paradigms that were developed to deliver novel antibacterial drugs as inhibitors of old and new essential bacterial targets proposed from single target to genome-wide initiatives. It also discusses some new trends in antibacterial discovery that have emerged with the rapid evolution and spread of antibiotic multi-resistances.

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Abbreviations

AS-RNA:

Antisense ribonucleic acid

AISS:

Antisense-induced strain sensitivity

A-KDO:

Keto-deoxyoctulosonate

ELT:

Encoded library technology

FAS:

Fatty acid synthesis

FBLD:

Fragment-based lead discovery

GlmU:

UDP-GlcNAc diphosphorylase/GlcNAc-1-P N-acetyltransferase

HTS:

High throughput screening

IPTG:

Isopropyl β-D-1-thiogalactopyranoside

LPS:

Lipopolysaccharide

LpxC:

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase

LtaS:

Lipoteichoic acid synthase

MOA:

Mode of action

MRSA:

Methicillin-resistant Staphylococcus aureus

MDRSA:

Multidrug-resistant Staphylococcus aureus

MIC:

Minimal inhibitory concentration

4MUA:

4-methylumbelliferyl acetate

NMR:

Nuclear magnetic resonance

OD:

Optical density

PDF:

Peptide deformylase

PgdA:

Peptidoglycan N-acetylglucosamine deacetylase A

pNPA:

P-nitrophenyl acetate

RNR:

Ribonucleotide reductase

SBDD:

Structure-based drug discovery

SOS:

Bacterial SOS response

UDP-gal:

Uridine diphosphate galactose

UDP-glucose:

Uridine diphosphate glucose

UPPS:

Undecaprenyl diphosphate synthase

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Authors and Affiliations

  1. Fundación MEDINA, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento 3, 18016, Granada, Spain

    Olga Genilloud & Francisca Vicente

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  1. Olga Genilloud
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  2. Francisca Vicente
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Correspondence to Olga Genilloud .

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  1. Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell'Insubria, Varese, Italy

    Flavia Marinelli

  2. Parque Tecnológico Ciencias de la Salud, Fundación MEDINA, Granada, Spain

    Olga Genilloud

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Genilloud, O., Vicente, F. (2014). Strategies to Discover Novel Antimicrobials to Cope with Emerging Medical Needs. In: Marinelli, F., Genilloud, O. (eds) Antimicrobials. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39968-8_17

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