The future challenges facing the development of new antimicrobial drugs

Coates, Anthony R. M.; Hu, Yan; Bax, Richard; Page, Clive

doi:10.1038/nrd940

Cited by 596 publications

(471 citation statements)

References 122 publications

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“…Furthermore, the narrow spectrum of the ranalexin with lysostaphin treatment reduces the opportunity for resistance to emerge in the normal bacterial flora, which is a mechanism recognised for the emergence and spread of resistance to pathogens [27]. Importantly, the present study shows that in combination ranalexin with lysostaphin is synergistically bactericidal against S. aureus strains with reduced susceptibility to lysostaphin, which is often characterised by mutation of the fem or lyrA genes [16,28].…”

Section: Discussionmentioning

confidence: 58%

In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections

Desbois¹,

Gemmell²,

Coote³

2010

International Journal of Antimicrobial Agents

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Section: Discussionmentioning

confidence: 58%

In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections

Desbois¹,

Gemmell²,

Coote³

2010

International Journal of Antimicrobial Agents

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“…The five main bacterial processes that are involved in the mechanisms of action for antibiotics include cell wall synthesis, protein synthesis, DNA synthesis, DNA‐directed RNA polymerase and essential metabolic enzymes (Coates et al , 2002). Based on the selectivity against different types of bacteria, antibiotics are divided into broad‐spectrum antibiotics that suppress a wide range of bacteria including both Gram‐positive and Gram‐negative and narrow‐spectrum antibiotics that are only active against small groups of bacteria, such as Gram‐negative or Gram‐positive bacteria.…”

Section: Discovery and Development Of New Antibiotics – Issues And Nementioning

confidence: 99%

Drug repurposing screens and synergistic drug‐combinations for infectious diseases

Zheng

Sun

Simeonov

2017

British J Pharmacology

221

200

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Infectious diseases account for nearly one fifth of the worldwide death toll every year. The continuous increase of drug‐resistant pathogens is a big challenge for treatment of infectious diseases. In addition, outbreaks of infections and new pathogens are potential threats to public health. Lack of effective treatments for drug‐resistant bacteria and recent outbreaks of Ebola and Zika viral infections have become a global public health concern. The number of newly approved antibiotics has decreased significantly in the last two decades compared with previous decades. In parallel with this, is an increase in the number of drug‐resistant bacteria. For these threats and challenges to be countered, new strategies and technology platforms are critically needed. Drug repurposing has emerged as an alternative approach for rapid identification of effective therapeutics to treat the infectious diseases. For treatment of severe infections, synergistic drug combinations using approved drugs identified from drug repurposing screens is a useful option which may overcome the problem of weak activity of individual drugs. Collaborative efforts including government, academic researchers and private drug industry can facilitate the translational research to produce more effective new therapeutic agents such as narrow spectrum antibiotics against drug‐resistant bacteria for these global challenges.Linked ArticlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc

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“…This extracellular matrix comprises 2/3 of the mass of the biofilm itself and acts as a protective barrier from the outside world [4]. The matrix confers resistance to penetration of antibiotics through the biofilm into the microbes [5,6]. Classically, biofilms were considered to be primarily associated with catheter or implant-associated infections, as well as dental plaques [7].…”

Section: Biofilm Formation Of P Acnesmentioning

confidence: 99%

The Role of Propionibacterium acnes Biofilm in Acne Vulgaris

Linfante¹,

Allawh²,

Allen³

2017

J Clin Exp Dermatol Res

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Acne vulgaris is traditionally known as the result of excess sebum production, follicular hyper keratinization, infection with Propionibacterium acnes, and follicular inflammation. However, the role of P. acnes is gaining momentum as the primary impetus in the pathogenesis of acne vulgaris. The biofilm-forming ability of P. acnes in vitro and on indwelling medical appliances and catheters has been known for quite some time, but only in the last decade has the presence of P. acnes biofilm been observed within the pilosebaceous unit. Since that time, the genome of the microbe has been sequenced, and genes responsible for quorum sensing and biofilm formation have been confirmed. As a result of biofilm formation, the virulence of P. acnes is amplified. Biofilm-encapsulated P. acnes upregulates the production of lipases, resulting in the production of free fatty acids. Free fatty acids as well as the biofilm itself bind the Toll-like receptors TLR2 and TLR4, activating the innate immune system, culminating in a robust inflammatory response. Biofilms also appear to significantly contribute to antibiotic resistance. Acting as a physical barrier for antibiotics as well as a commune for bacteria to exchange antibiotic resistance genes, the biofilm plays an integral role as the major hurdle to treating acne vulgaris. Traditional antimicrobials have not shown much promise in disruption of the biofilm. Other approaches have been investigated utilizing a variety of novel topical compounds that act to prevent or disrupt the biofilm as a therapeutic modality. The role of biofilm in the pathogenesis of acne vulgaris has remained underappreciated, but with global antimicrobial resistance looming, further attention may be warranted.

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The future challenges facing the development of new antimicrobial drugs

Cited by 596 publications

References 122 publications

In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections

In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections

Drug repurposing screens and synergistic drug‐combinations for infectious diseases

The Role of Propionibacterium acnes Biofilm in Acne Vulgaris

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