Targeting Antibiotic Resistance

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Abstract

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

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Most cited references 124

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Transcription factors: from enhancer binding to developmental control.

François Spitz, Eileen E M Furlong (2012)

Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development.

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Siderophore-based iron acquisition and pathogen control.

Marcus Miethke, Mohamed A. Marahiel (2007)

High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as "Trojan horse" toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.

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Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications.

Roland Leclercq (2002)

Resistance to macrolides and lincosamides is increasingly reported in clinical isolates of gram-positive bacteria. The multiplicity of mechanisms of resistance, which include ribosomal modification, efflux of the antibiotic, and drug inactivation, results in a variety of phenotypes of resistance. There is controversy concerning the clinical relevance of in vitro macrolide resistance. Recent data, however, have shown that eradication of bacteria correlates with clinical outcome of acute otitis media in children and that macrolide therapy results in delayed eradication of macrolide-resistant pneumococci. These results support the need for in vitro detection of macrolide resistance and correct interpretation of susceptibility tests to guide therapy.

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Author and article information

Contributors

Prof. Dr. Rainer Riedl:

ORCID: http://orcid.org/0000-0003-2534-1963

rainer.riedl@zhaw.ch

Journal

Journal ID (nlm-ta): Angew Chem Int Ed Engl

Journal ID (iso-abbrev): Angew. Chem. Int. Ed. Engl

Journal ID (doi): 10.1002/(ISSN)1521-3773

Journal ID (publisher-id): ANIE

Title: Angewandte Chemie (International Ed. in English)

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1433-7851

ISSN (Electronic): 1521-3773

Publication date (Electronic): 22 March 2016

Publication date (Print): 01 June 2016

Volume: 55

Issue: 23 ( doiID: 10.1002/anie.v55.23 )

Pages: 6600-6626

Affiliations

[ ¹ ] Institute of Chemistry and Biotechnology Center for Organic and Medicinal ChemistryZurich University of Applied Sciences (ZHAW) Einsiedlerstrasse 31 8820 WädenswilSwitzerland

Author information

Dr. Mathieu F. Chellat http://orcid.org/0000-0002-3802-672X

Luka Raguž http://orcid.org/0000-0001-5383-3012

Prof. Dr. Rainer Riedl http://orcid.org/0000-0003-2534-1963

Article

Publisher ID: ANIE201506818

DOI: 10.1002/anie.201506818

PMC ID: 5071768

PubMed ID: 27000559

SO-VID: e7b31d9d-eb9f-42e5-9292-ab1481b0170d

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date received : 23 June 2015

Date revision received : 10 October 2015

Page count

Figures: 46, Tables: 0, References: 203, Pages: 27

Funding

Funded by: Swiss Commission for Technology and Innovation (CTI)

Award ID: CTI-11601.1 PFLS-LS

Award ID: CTI-12667.1 PFLS-LS

Award ID: CTI-15235.1 PFLS-LS

Award ID: CTI-16445.1 PFLS-LS

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source-schema-version-number 2.0

component-id anie201506818

cover-date June 1, 2016

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.5 mode:remove_FC converted:20.10.2016

ScienceOpen disciplines: Chemistry

Keywords: antibiotics,antibiotic resistance,drug design,medicinal chemistry,structure–activity relationships

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ScienceOpen disciplines: Chemistry

Keywords: antibiotics, antibiotic resistance, drug design, medicinal chemistry, structure–activity relationships

Targeting Antibiotic Resistance

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Abstract

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Microbiology Independent Research Journal (MIR Journal)

Most cited references 124

Transcription factors: from enhancer binding to developmental control.

Siderophore-based iron acquisition and pathogen control.

Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications.

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