Two different pharmacophoric domains attached covalently by a linker domain. Two different pharmacophoric domains attached covalently by a linker domain.

Slides:



Advertisements
Similar presentations
Overview of potential risk or protective factors influencing the horizontal or vertical transmission of Neospora caninum and the occurrence of exogenous.
Advertisements

Itraconazole tissue and fluid concentrations in humans as multiples of the maximal or simultaneously measured concentration in plasma (μg/ml) after systemic.
Characteristic stacked-brick pattern observed when EAEC is cultured on HEp-2 cells. Characteristic stacked-brick pattern observed when EAEC is cultured.
Voriconazole tissue and fluid concentrations in humans as multiples of the maximal or simultaneously measured concentration in plasma (μg/ml) after systemic.
Cross section of the brain of a mouse with cryptococcal meningoencephalitis. Cross section of the brain of a mouse with cryptococcal meningoencephalitis.
Mechanisms by which microbial cells might develop resistance
Frequency of lesions detected using CNS imaging (computed tomography [CT] and magnetic resonance imaging [MRI]) on patients with baylisascariasis (see.
The human norovirus genome.
Characterization of oprD promoter elements.
Phylogenetic tree showing generic and species positions based on Bayesian analysis of the nuclear ribosomal DNA 28S region (1,200 bp) of Schistosomatidae.
Interaction of drug substrates and the AcrB-binding protomer analyzed with Autodock Vina docking software. Interaction of drug substrates and the AcrB-binding.
Electron micrographs of the binding of human vitronectin to complement-resistant (left) and complement-sensitive (right) strains of M. catarrhalis. Electron.
Scheme of dynamic SCV development in the course from acute to chronic infection. Scheme of dynamic SCV development in the course from acute to chronic.
Columbia blood agar plate showing an isogenic S
Approximate numbers of cases per 100,000 individuals caused by penicillin resistance for each year (left). Approximate numbers of cases per 100,000 individuals.
MexT-associated downregulation of oprD expression.
Relative abundances of Propionibacterium species in different skin areas determined by 16S rRNA gene sequence analysis of 10 individuals. Relative abundances.
Comparative analysis of C. glabrata, C. albicans, and S
Glucose concentration-dependent increase of melanin synthesis.
Detection of Ebola virus infection in nonfatal versus fatal cases.
Increasing prevalence of multidrug resistance among P
Phylogenetic tree of intestinal pathogenic E. coli.
Transmission electron micrograph of M
Fluconazole tissue and fluid concentrations in humans as multiples of the maximal or simultaneously measured concentration in plasma (μg/ml) after systemic.
Number of outbreaks associated with drinking water by water system type and year (n = 780), 1971 to “Other” includes outbreaks associated with bottled.
Percentages of outbreak deficiencies (n = 671) in public water systems (n = 656) by time period, 1971 to 2006, excluding outbreaks associated with Legionella.
Mechanism of macrophage apoptosis caused by H. pylori.
Potentiation of legacy antibiotics against P
Phylogenetic network with concatenated 16S rRNA, 23S rRNA, groEL, rpoB, and dnaK sequences (3,009 unambiguously aligned base pairs), including 71 Coxiella-like.
Examples of antibiotic hybrid drugs that are active against Gram-negative pathogens: trimethoprim linked to ciprofloxacin–BP-4Q-002 (hybrid 5), the TyrRS.
Drug transport mechanism of AcrB.
Β-Lactam hydrolysis of cephalosporin followed by nonenzymatic release of a leaving group (LG). β-Lactam hydrolysis of cephalosporin followed by nonenzymatic.
(Top) Graph illustrating citations in books for Plasmodium falciparum and Plasmodium vivax from 1900 to 2008, generated by use of the tool at
Examples of advanced hybrid antibiotics undergoing clinical trials: cadazolid (hybrid 17) and TNP-2092, also known as CBR-2092 (hybrid 18). Examples of.
Number of outbreaks associated with drinking water by system type and month (n = 762), 1971 to 2006, excluding outbreaks associated with commercially bottled.
Summary of the distribution and genetic context of the OXA-type enzymes in Acinetobacter baumannii. Summary of the distribution and genetic context of.
Fabrizio Dutly, and Martin Altwegg Clin. Microbiol. Rev. 2001; doi:10
Shell vial system protocols used for specific isolation of Bartonella, Coxiella burnetii, rickettsiae, or T. whipplei and for unspecific research into.
Schematic model of the cell envelope of M. leprae.
Staphylococcus aureus and Staphylococcus epidermidis cell surface proteins, known as microbial surface components recognizing adhesive matrix molecules.
Structure of cefiderocol (hybrid 10), previously known as S , derived by linking ceftazidime to the siderophore catechol 2-chloro-3,4-dihydroxybenzoic.
Examples of tobramycin-efflux pump hybrids: tobramycin linked to 1-(1-naphthylmethyl)-piperazine (NMP) (hybrid 14), tobramycin linked to paroxetine (hybrid.
Hector H. García et al. Clin. Microbiol. Rev. 2002; doi: /CMR
Publications on biosensors for the field in general compared with the specific detection of whole bacteria. Publications on biosensors for the field in.
Serial testing with IGRAs reveals underlying phenotypes.
Roberta B. Carey et al. Clin. Microbiol. Rev. 2018; doi: /CMR
Various possible courses of the immune response to severe sepsis and septic shock over 28 days. Various possible courses of the immune response to severe.
Schematic representation of 5′→3′ exonuclease cleavage of a 5′-labeled (small black star) probe with a 3′-phosphate (grey circle) extension blocker. Schematic.
General schematic for the identification of bacteria and yeast by MALDI-TOF MS using the intact-cell method. General schematic for the identification of.
Synchronization of a basic diagnostic algorithm (linked diagnostic tests) with different levels of diagnostic services. Synchronization of a basic diagnostic.
Stages of biofilm development (214).
The future TB clinic. The future TB clinic. Sputum, saliva, and fecal samples are collected from patients for genome sequencing, SNP typing, or metagenomic.
Percentages of outbreak deficiencies in public water systems associated with untreated and improperly treated source water by year, 1971 to 2006, excluding.
Giemsa-stained thin blood smears from a nonobese diabetic (NOD)-SCID mouse infected with (A) B. microtistrain MN1, (B) a hamster infected with B. microti.
Number of ESBL carriers in the community in 2010, according to WHO region grouping. Number of ESBL carriers in the community in 2010, according to WHO.
The Scorpions primer is an extension of molecular beacons.
Structure and function of RND efflux pumps in P. aeruginosa.
Phylogenetic trees for fusion (F) and attachment (G) genes of selected HMPV isolates. Phylogenetic trees for fusion (F) and attachment (G) genes of selected.
Fluconazole zone diameter distributions for all Candida spp
Adherence patterns of enteropathogenic E
Relationship between MIC, dose of fluconazole, and emergence/expression of specific resistance mechanisms in oropharyngeal candidiasis. •, MIC of fluconazole.
Outcomes of infections caused by carbapenemase-producing Klebsiella pneumoniae, according to treatment regimen. Outcomes of infections caused by carbapenemase-producing.
Phylogenetic tree of the complete genomes of 27 representative human (black) and camel (red) MERS-CoV strains rooted by NeoCoV (KC ). Phylogenetic.
Biofilm types. Biofilm types. (A) Surface-attached biofilms form colonies on a solid surface and are highly dependent on the substratum material. (B) Pellicles.
Distribution of the four major molecular types of C
Schematic representation of the relationships between acid resistance (urease activity and urea transport), nitrogen metabolism (ammonia production), metal.
Effects of acute malnutrition on lymphoid and hematopoietic organs.
Diagrammatic view of the locations of genes encoding classical HLA class I (HLA-A, -B, -C, -E, -F, and -G) and class II (DR, DQ, DP, and DM) molecules.
Proposed United Nations “One Health” framework.
Amino acid substitutions in SHV ESBL derivatives.
Presentation transcript:

Two different pharmacophoric domains attached covalently by a linker domain. Two different pharmacophoric domains attached covalently by a linker domain. The lability of the linker determines the type of antibiotic hybrid generated. A linker that can be enzymatically degraded (preferably by only bacterium-specific enzymes) gives rise to two functional pharmacophoric entities that are thus used in the antibiotic hybrid prodrug strategy. A linker that is inert to enzymatic degradation is used to hold the two pharmacophoric domains together in the antibiotic hybrid drug strategy. Ronald Domalaon et al. Clin. Microbiol. Rev. 2018; doi:10.1128/CMR.00077-17