Antibiotic resistance: global response needed

Howard, Simon; Catchpole, Mike; Watson, John T.; Davies, Sally C.

doi:10.1016/s1473-3099(13)70195-6

Cited by 68 publications

(50 citation statements)

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“…61,62 The development of rapid point-of-care diagnostic tools may be of use to reduce clinical uncertainty, to save unnecessary antibiotic treatments, and to select effective antibiotics where resistance has rendered first-line treatment ineffective. 63 The recent discovery of a new antibiotic called teixobactin, with excellent activity against Grampositive pathogens, including drug-resistant strains, represents a hope for the future and an example for new researches. 64 …”

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confidence: 99%

Antimicrobial resistance: a global multifaceted phenomenon

Prestinaci

Pezzotti

Pantosti

2015

Pathogens and Global Health

2,077

1,370

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Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern -Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis -for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.

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confidence: 99%

Antimicrobial resistance: a global multifaceted phenomenon

Prestinaci

Pezzotti

Pantosti

2015

Pathogens and Global Health

2,077

1,370

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“…The ability of microbes to develop resistance to cytotoxic drugs, and to adapt rapidly to changes in the exposure to these compounds is an extremely important medical problem1. Drug resistance can be specific for a single drug or class of drugs, or occur simultaneously for a wide variety of toxic compounds that are structurally and functionally unrelated.…”

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confidence: 99%

Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions

Nair

Singh

Raturi

et al. 2016

Sci Rep

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The expression of polyspecific membrane transporters is one important mechanism by which cells can obtain resistance to structurally different antibiotics and cytotoxic agents. These transporters reduce intracellular drug concentrations to subtoxic levels by mediating drug efflux across the cell envelope. The major facilitator superfamily multidrug transporter LmrP from Lactococcus lactis catalyses drug efflux in a membrane potential and chemical proton gradient-dependent fashion. To enable the interaction with protons and cationic substrates, LmrP contains catalytic carboxyl residues on the surface of a large interior chamber that is formed by transmembrane helices. These residues colocalise together with polar and aromatic residues, and are predicted to be present in two clusters. To investigate the functional role of the catalytic carboxylates, we generated mutant proteins catalysing membrane potential-independent dye efflux by removing one of the carboxyl residues in Cluster 1. We then relocated this carboxyl residue to six positions on the surface of the interior chamber, and tested for restoration of wildtype energetics. The reinsertion at positions towards Cluster 2 reinstated the membrane potential dependence of dye efflux. Our data uncover a remarkable plasticity in proton interactions in LmrP, which is a consequence of the flexibility in the location of key residues that are responsible for proton/multidrug antiport.The ability of microbes to develop resistance to cytotoxic drugs, and to adapt rapidly to changes in the exposure to these compounds is an extremely important medical problem 1 . Drug resistance can be specific for a single drug or class of drugs, or occur simultaneously for a wide variety of toxic compounds that are structurally and functionally unrelated. The latter phenomenon is called multidrug resistance, and is recognised as an important mechanism of bacterial resistance to valuable clinical antibiotics. In many cases, the development of multidrug resistance is due to the enhanced expression levels of drug pumps in the cell 2 . These pumps mediate the extrusion of antimicrobials across the cell envelope, away from intracellular targets. Enzyme-ligand interactions are usually based on very specific interactions that allow discrimination between enantiomers of the same ligand. The ability of multidrug transporters to recognise a broad spectrum of structurally unrelated drugs is intriguing.Multidrug transporters have been reinvented on multiple occasions in the course of evolution, and are found in six different protein families: the ATP-binding cassette (ABC) superfamily, resistance-nodulation-cell division (RND) family, multiple antibiotics and toxin extrusion (MATE) family, small multidrug resistance (SMR) family, proteobacterial antimicrobial compound efflux (PACE) family, and major facilitator superfamily (MFS) 3,4 . It is generally accepted that members of the ABC family couple drug efflux to ATP binding and hydrolysis, whereas the members of the other 5 families operate by a secon...

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“…[6][7][8] However, the gut and skin are principally composed of commensal bacteria outnumbering the pathogenic bacteria by several orders of magnitude. Targeted delivery via complementary antibodies is one way to retain the commensal population, reduce recovery times, and guard against secondary infections.…”

Section: Cancer Imaging and Therapeuticsmentioning

confidence: 99%

Spotlight on nano-theranostics in South Korea: applications in diagnostics and treatment of diseases

Lee¹,

Kim²,

Bark³

et al. 2015

IJN

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From the synergistic integration and the multidisciplinary strengths of the BioNano Sensor Research Center, Gachon Bionano Research Institute, and Lee Gil Ya Cancer and Diabetes Institute, researchers, students, and faculties at Gachon University in collaboration with other institutions in Korea, Australia, France, America, and Japan have come together to produce a special issue on the diverse applications of nano-theranostics in nanomedicine. This special issue will showcase new research conducted by various scientific groups in Gyonggi-do and Songdo/Incheon, South Korea. The objectives of this special issue are as follows: 1) to bring together and demonstrate some of the latest research results in the field, 2) to introduce new multifunctional nanomaterials and their applications in imaging and detection methods, and 3) to stimulate collaborative interdisciplinary research at both national and international levels in nanomedicine.

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Antibiotic resistance: global response needed

Cited by 68 publications

References 1 publication

Antimicrobial resistance: a global multifaceted phenomenon

Antimicrobial resistance: a global multifaceted phenomenon

Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions

Spotlight on nano-theranostics in South Korea: applications in diagnostics and treatment of diseases

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Antibiotic resistance: global response needed

Cited by 68 publications

References 1 publication

Antimicrobial resistance: a global multifaceted phenomenon

Antimicrobial resistance: a global multifaceted phenomenon

Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions

Spotlight on nano-theranostics in South Korea: applications in diagnostics and treatment of&nbsp;diseases

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Spotlight on nano-theranostics in South Korea: applications in diagnostics and treatment of diseases