Genesis of Antibiotic Resistance (AR) LXXIV: Turbulence Modeling of Simplified Severe Sepsis Protocol‐2 (SSSP‐2), NCT01663701: Mechanism of Torque on E‐Cpx Thrusted Leucocyte(s)‐Platelet(s)‐Erythrocyte(s) Aggregates’ (LPE) drag on capillary lumen ace Elicit Irreversible Occlusion‐CCP‐Coma,
            Impediments for in vivo Simulation

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

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Artificial Klebsiella pneumoniae biofilm model mimicking in vivo system: altered morphological characteristics and antibiotic resistance

The Journal of Antibiotics ◽

10.1038/ja.2013.139 ◽

2014 ◽

Vol 67 (4) ◽

pp. 305-309 ◽

Cited By ~ 10

Author(s):

Saloni Singla ◽

Kusum Harjai ◽

Sanjay Chhibber

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Morphological Characteristics ◽

Biofilm Model

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Clinically Relevant Antibiotic Resistance Mechanisms Can Enhance the In Vivo Fitness of Neisseria gonorrhoeae

Antibiotic Resistant Bacteria - A Continuous Challenge in the New Millennium ◽

10.5772/29449 ◽

2012 ◽

Author(s):

Elizabeth A. ◽

Jonathan A. ◽

Anjali N. ◽

Ann E. ◽

William M.

Keyword(s):

Antibiotic Resistance ◽

Neisseria Gonorrhoeae ◽

Resistance Mechanisms

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Clinical extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can spread in the absence of antibiotic selection

10.1101/796243 ◽

2019 ◽

Cited By ~ 4

Author(s):

Fabienne Benz ◽

Jana S. Huisman ◽

Erik Bakkeren ◽

Joana A. Herter ◽

Tanja Stadler ◽

...

Keyword(s):

Antibiotic Resistance ◽

Conjugative Transfer ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Resistance Plasmids ◽

Serovar Typhimurium ◽

Spreading Potential

AbstractHorizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinical Escherichia coli strains natively associated with ESBL-plasmids conjugate efficiently with three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hours in vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spread in vitro and in vivo. This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based on in vitro testing. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.

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High throughput functional variant screens via in-vivo production of single-stranded DNA

10.1101/2020.03.05.975441 ◽

2020 ◽

Cited By ~ 2

Author(s):

Max G. Schubert ◽

Daniel B. Goodman ◽

Timothy M. Wannier ◽

Divjot Kaur ◽

Fahim Farzadfard ◽

...

Keyword(s):

Antibiotic Resistance ◽

High Throughput ◽

Entire Genome ◽

Single Stranded Dna ◽

Functional Variant ◽

Continuous Generation ◽

Sources Of Variation ◽

Targeted Deep Sequencing ◽

High Throughput Screens

AbstractTremendous genetic variation exists in nature, but our ability to create and characterize individual genetic variants remains far more limited in scale. Likewise, engineering proteins and phenotypes requires the introduction of synthetic variants, but design of variants outpaces experimental measurement of variant effect. Here, we optimize efficient and continuous generation of precise genomic edits in Escherichia coli, via in-vivo production of single-stranded DNA by the targeted reverse-transcription activity of retrons. Greater than 90% editing efficiency can be obtained using this method, enabling multiplexed applications. We introduce Retron Library Recombineering (RLR), a system for high-throughput screens of variants, wherein the association of introduced edits with their retron elements enables a targeted deep sequencing phenotypic output. We use RLR for pooled, quantitative phenotyping of synthesized variants, characterizing antibiotic resistance alleles. We also perform RLR using sheared genomic DNA of an evolved bacterium, experimentally querying millions of sequences for antibiotic resistance variants. In doing so, we demonstrate that RLR is uniquely suited to utilize non-designed sources of variation. Pooled experiments using ssDNA produced in vivo thus present new avenues for exploring variation, both designed and not, across the entire genome.

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