Horizontal gene transfert and antibiotic resistance
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Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa

Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa | Horizontal gene transfert and antibiotic resistance | Scoop.it
Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies.
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Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent Clostridium difficile infection

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Novel antibody–antibiotic conjugate eliminates intracellular S. aureus

Novel antibody–antibiotic conjugate eliminates intracellular S. aureus | Horizontal gene transfert and antibiotic resistance | Scoop.it

Abstract


Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureuswithin host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody–antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody–antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureusrepresents an important component of invasive infections.

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Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure - EBioMedicine

Host-dependent Induction of Transient Antibiotic Resistance: A Prelude to Treatment Failure - EBioMedicine | Horizontal gene transfert and antibiotic resistance | Scoop.it

Standard MIC testing does not consider the influence of the host milieu, potentially hindering therapeutic intervention.

Salmonella induce polymyxin resistance during infection at levels of drug that far exceed dosages determined by MIC testing.

Polymyxin treatment failed to control Salmonella infection and promotes the emergence of drug-resistant mutants.

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EFSA - Scientific Report of EFSA: Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report

EFSA - Scientific Report of EFSA: Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report | Horizontal gene transfert and antibiotic resistance | Scoop.it
The ECDC, the EFSA and the EMA have for the first time jointly explored associations between consumption of antimicrobials in humans and food-producing animals, and antimicrobial resistance in bacteria from humans and food-producing animals, using 2011 and 2012 data currently available from their relevant five EU monitoring networks. Combined data on antimicrobial consumption and corresponding resistance in animals and humans for EU MSs and reporting countries were analysed using logistic regres
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Policy: An intergovernmental panel on antimicrobial resistance

Policy: An intergovernmental panel on antimicrobial resistance | Horizontal gene transfert and antibiotic resistance | Scoop.it
Drug-resistant microbes are spreading.
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WHO | WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health

New WHO report provides the most comprehensive picture of antibiotic resistance to date, with data from 114 countries
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Large-Scale Metagenomic-Based Study of Antibiotic Resistance in the Environment: Current Biology

Large-Scale Metagenomic-Based Study of Antibiotic Resistance in the Environment: Current Biology | Horizontal gene transfert and antibiotic resistance | Scoop.it

"Using metagenomic sequences, we show that antibiotic resistance gene determinants (ARGDs) can be detected in all (n = 71) environments analyzed. Soil metagenomes had the most diverse pool of ARGDs. The most common types of resistances found in environmental metagenomes were efflux pumps and genes conferring resistance to vancomycin, tetracycline, or β-lactam antibiotics used in veterinary and human healthcare. Our study describes the diverse and abundant antibiotic resistance genes in nonclinical environments and shows that these genes are not randomly distributed among different environments (e.g., soil, oceans or human feces)."

Maria-H Laaberki's insight:

Thus the need to understand how bacteria acquire them.

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Survival of A. baumannii in municipal wastewater (Croatia)

Survival of A. baumannii in municipal wastewater (Croatia) | Horizontal gene transfert and antibiotic resistance | Scoop.it
Acinetobacter baumannii is an emerging hospital pathogen. Whereas A. baumannii isolated from patients or hospitals has been reported, there are few data regarding propagation of viable A. baumannii in the natural environment. This study investigates the occurrence and antimicrobial susceptibility of viable A. baumannii in municipal wastewater and its persistence through the wastewater treatment process. A total of 21 A. baumannii isolates were recovered at a secondary type of municipal wastewater treatment plant in Zagreb, Croatia: 15 from raw influent wastewater and six from final effluent. All isolates were carbapenem- and multidrug-resistant. Among 14 isolates tested for blaOXA genes, all harboured the constitutive blaOXA-51-like gene, while the acquired blaOXA-23-like and blaOXA-40-like genes were found in 10 and three isolates respectively. Six A. baumannii isolates recovered from effluent wastewater multiplied and survived in sterilised effluent wastewater up to 50 days. These findings support the idea that multidrug-resistant A. baumannii can occur and have the ability to survive in the environment.
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Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study - The Lancet Infectious Diseases

Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.

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First description plasmid-mediated polymyxin resistance mechanism in E. coli detected in humans and animals.

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The State of the World's Antibiotics, 2015 | Center for Disease Dynamics, Economics & Policy (CDDEP)

The State of the World's Antibiotics, 2015 | Center for Disease Dynamics, Economics & Policy (CDDEP) | Horizontal gene transfert and antibiotic resistance | Scoop.it
Maria-H Laaberki's insight:

What is the current state of antibiotic use and resistance in humans and animals around the globe? In low- and middle-income countries? What national-level strategies can help countries combat antibiotic resistance? 


An alarming look at antibiotic resistance.

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Fitness cost of antibiotic susceptibility during bacterial infection

Fitness cost of antibiotic susceptibility during bacterial infection | Horizontal gene transfert and antibiotic resistance | Scoop.it
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A new antibiotic kills pathogens without detectable resistance

A new antibiotic kills pathogens without detectable resistance | Horizontal gene transfert and antibiotic resistance | Scoop.it

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosisresistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

Maria-H Laaberki's insight:

Teixobactin: a new natural antibiotic discovered in a screen of uncultured bacteria from marine dirt. Teixobactin, a depsipeptide, inhibits cell wall synthesis.

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A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria

Maria-H Laaberki's insight:

Many environmental bacteria are multidrug-resistant and represent a reservoir of ancient antibiotic resistance determinants, which have been linked to genes found in pathogens. Exploring the environmental antibiotic resistome, therefore, reveals the diversity and evolution of antibiotic resistance and also provides insight into the vulnerability of clinically used antibiotics. In this study, we describe the identification of a highly conserved regulatory motif, the rifampin (RIF) -associated element (RAE), which is found upstream of genes encoding RIF-inactivating enzymes from a diverse collection of actinomycetes. Using gene expression assays, we confirmed that the RAE is involved in RIF-responsive regulation. By using the RAE as a probe for new RIF-associated genes in several actinomycete genomes, we identified a heretofore unknown RIF resistance gene, RIF phosphotransferase (rph). The RPH enzyme is a RIF-inactivating phosphotransferase and represents a new protein family in antibiotic resistance. RPH orthologs are widespread and found in RIF-sensitive bacteria, including Bacillus cereus and the pathogen Listeria monocytogenes. Heterologous expression and in vitro enzyme assays with purified RPHs from diverse bacterial genera show that these enzymes are capable of conferring high-level resistance to a variety of clinically used rifamycin antibiotics. This work identifies a new antibiotic resistance protein family and reinforces the fact that the study of resistance in environmental organisms can serve to identify resistance elements with relevance to pathogens.

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Antibiotic-Resistant Germs, Lying in Wait Everywhere

A study finds that genes that let bacteria survive drugs intended to wipe them out are widespread, even in the most isolated parts of the planet.
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Concerted Spatio-Temporal Dynamics of Imported DNA and ComE DNA Uptake Protein during Gonococcal Transformation

Concerted Spatio-Temporal Dynamics of Imported DNA and ComE DNA Uptake Protein during Gonococcal Transformation | Horizontal gene transfert and antibiotic resistance | Scoop.it
From molecules to physiology
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DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related : Scientific Reports : Nature Publishing Group

DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related : Scientific Reports : Nature Publishing Group | Horizontal gene transfert and antibiotic resistance | Scoop.it
The human gut is a reservoir for antibiotic resistance genes. In this report, we used a DNA microarray chip covering 369 resistance types to investigate the relationship between antibiotic resistance-gene diversity and human age. Metagenomic DNA from fecal samples from 124 healthy volunteers of four different age groups (pre-school-aged children (CH), school-aged children (SC), high school students (HSS) and adults (AD)) were hybridized to the microarray chip. The results showed that 80 different gene types were recovered from the gut microbiota of the 124 individuals: 25 from CH, 37 from SC, 58 from HSS and 72 from AD. Further analysis indicated that the antibiotic resistance genes in the CH, SC and AD groups clustered independently, whereas the gene types in the HSS group were more divergent. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate from childhood to adulthood and become more complex with age.
Maria-H Laaberki's insight:

Not surprising but totally worth investigating

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