Resist 78 pdf

White WRN65 Impact-resistant. Clear Impact-resistant. Clear 0RS30 Impact-resistant. Diffuse 0RS09D Impact-resistant. White WRS30 Impact-resistant.

Grey 7RS30 Impact-resistant. White WRS19 Impact-resistant. Grey 7RS01 Impact-resistant. Clear 0A Smooth Impact-resistant. Clear 0A W Impact-resistant.

Clear 0A C Impact-resistant. Grey 7RW01 Smooth Impact-resistant. There are also practical issues of preventing the further increase in multidrug resistant bacteria.

Because the usage of antibiotics was the cause of selection of these bacteria, one logical conclusion is to minimize antibiotic usage. Simultaneous administration of more than one agent as is done with tuberculosis may be considered. For example, an inhibitor of multidrug efflux pumps lowers the MICs of various drugs strongly in gram-negative bacteria and may prevent the emergence of resistant organisms I thank colleagues for reading parts of this manuscript and for giving me the original figures for reproduction.

I apologize to authors whose studies could not be cited because of size limitations. The work in the author's laboratory has been supported by a research grant from U. National Institutes of Health AI National Center for Biotechnology Information , U.

Annu Rev Biochem. Author manuscript; available in PMC Mar Hiroshi Nikaido. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Annu Rev Biochem.

See other articles in PMC that cite the published article. Abstract Large amounts of antibiotics used for human therapy, as well as for farm animals and even for fish in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs.

Keywords: R plasmids, transposons, integrons, type IV secretion system, multidrug efflux pumps. Mutational Alteration of the Target Protein Man-made compounds, such as fluoroquinolones, are unlikely to become inactivated by the enzymatic mechanisms described below. Aminoglycosides Aminoglycosides are inactivated by modifications that reduce the net positive charges on these polycationic antibiotics 7 , 8. Acquisition of Genes for Less Susceptible Target Proteins from Other Species Sequencing of the genes coding for the targets of penicillin, DD-transpeptidase or penicillin-binding proteins PBPs , revealed that penicillin resistance among Streptococcus pneumoniae was due to the production of mosaic proteins, parts of which came from other organisms Bypassing of the Target Vancomycin, a fermentation product from streptomycetes, has an unusual mode of action.

Preventing Drug Access to Targets Drug access to the target can be reduced locally. Local inhibition of drug access Tet M or Tet S proteins, produced by plasmid-coded genes in gram-positive bacteria, bind to ribosomes with high affinity and apparently change the ribosomal conformation, thereby preventing the association of tetracyclines to ribosomes Drug-specific efflux pumps Drug resistance owing to active efflux was discovered with the common tetracycline resistance protein TetA in gram-negative bacteria 23 , which catalyze a proton-motive-force-dependent outward pumping of a tetracycine-Mg complex Producing Organisms As described above, some of the aminoglycoside-resistant genes appear to be derived from streptomycetes producing these antibiotics.

Microorganisms in the Environment, Especially Soil Some resistance genes are found in the chromosome of environmental bacteria. Assembly of Resistance Genes in R Plasmids We have seen that most drug resistance genes are effective when expressed from plasmids.

Open in a separate window. Figure 1. Figure 2. Maintenance of R Plasmids in the Host Cells Recombinant plasmids derived from cloning vectors are frequently lost from the host cells even when they exist in relatively high copy numbers. Figure 3. Figure 4. Structures and possible mechanisms of these transporters have been reviewed recently 49 Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily MFS is one of the largest families of transporters and contains many important efflux pumps.

Multidrug Efflux Pumps of Resistance-Nodulation-Division Family Transporters of this family play, by far, a predominant role in the multidrug resistance of gram-negative bacteria. Resistance-nodulation-division pump usually exists as a part of a tripartite complex Efflux pumps of this superfamily such as AcrB of E.

Figure 5. Sources for the data can be found in 47 , 79 as well as in the text. Biochemical and crystallographic studies Biochemical studies of the RND-type efflux pumps were hampered by the fact that the pumps function as multiprotein complexes spanning two membranes. Figure 6. Figure 7. Contributions of RND efflux pumps to the resistance in clinical strains RND pumps are making major contributions both to the intrinsic and elevated resistance of clinically relevant pathogens RND transporters that pump out nondrug substrates Some of the RND transporters are involved in the export of compounds other than the antimicrobials.

Glossary MRSA methicillin-resistant Staphylococcus aureus Aminoglycosides bactericidal antibiotics that are active against those gram-negative bacteria, resisting most other antibiotics owing to their low permeability outer membrane Transposons discrete DNA sequences that can move to another sites.

Antibiotic resistant Staphylococcus aureus : a paradigm of adaptive power. Livermore DM. The need for new antibiotics. Hooper DC. Mechanisms of action and resistance of older and newer fluoroquinolones. Weisblum B. Erythromycin resistance by ribosome modification. Agents Chemother. Poehlsgaard J, Douthwaite S.

The bacterial ribosome as a target for antibiotics. Trimethoprim and sulfonamide resistance. Davies J, Wright GD. Bacterial resistance to aminoglycoside antibiotics. Trends Microbiol. Wright GD. Aminoglycoside-modifying enzymes. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.

Benveniste R, Davies J. Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey. Datta N, Kontomichalou P. Penicillinase synthesis controlled by infectious R factors in Enterobacteriaceae. Vu H, Nikaido H. Bonnet R. High rate of mobilization for bla CTX-M s.

Queenan AM, Bush K. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Spratt BG. Resistance to antibiotics mediated by target alterations.

Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Ribosomal protection proteins and their mechanism of tetracycline resistance. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect. Levy SB. Active efflux mechanisms for antimicrobial resistance. Multiple facets of bacterial porins. FEMS Microbiol. Glycopeptide antibiotic resistance genes in glycopeptide-producing organisms.

Sampling the antibiotic resistome. Bacteria subsisting on antibiotics. Facile recovery of individual high-molecular-weight, low-copy-number natural plasmids for genomic sequencing.

Transposon Tn 21 , flagship of the floating genome. Integrons: novel DNA elements which capture genes by site-specific recombination. The role of integrons in antibiotic resistance gene capture. Mazel D. Integrons: agents of bacterial evolution. IS CR elements: novel gene-capturing systems of the 21st century?

Nordstrom K, Austin SJ. Mechanisms that contribute to the stable segregation of plasmids. Uniform nomenclature for bacterial plasmids: a proposal. Plasmids studied in Escherichia coli and in other enteric bacteria. Cold Spring Harb. The mating pair formation system of conjugative plasmids—A versatile secretion machinery for transfer of proteins and DNA.

Biogenesis, architecture, and function of bacterial type IV secretion systems. Lessl M, Lanka E. Lateral gene transfer and the nature of bacterial innovation. Conjugative plasmid transfer in gram-positive bacteria. Rice LB. Tn family conjugative transposons and dissemination of antimicrobial resistance determinants. Courvalin P. The Garrod Lecture: evasion of antibiotic action by bacteria. Proton-dependent multidrug efflux systems. Li XZ, Nikaido H.

Efflux-mediated drug resistance in bacteria. Poole K. Efflux-mediated antimicrobial resistance. Higgins CF. Multiple molecular mechanisms for multidrug resistance transporters. Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factors. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity.

Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein. EMBO J. Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB in multiple positions. Crystal structures of multidrug binding protein TtgR in complex with antibiotics and plant antimicrobials.

Lomovskaya O, Lewis K. Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter. NorC, a new efflux pump regulated by MgrA of Staphylococcus aureus. Efflux-related resistance to norfloxacin, dyes, and biocides in bloodstream isolates of Staphylococcus aureus.

Energetics of wild-type and mutant multidrug resistance secondary transporter LmrP of Lactococcus lactis. Nishino K, Yamaguchi A.

Analysis of a complete library of putative drug transporter genes in Escherichia coli. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Structure of the multidrug transporter EmrD from Escherichia coli.

The SMR family: a novel family of multidrug efflux proteins involved with the efflux of lipophilic drugs. Small is mighty: EmrE, a multidrug transporter as an experimental paradigm. News Physiol. Schuldiner S. When biochemistry meets structural biology: the cautionary tale of EmrE. Trends Biochem. Quasi-symmetry in the cryo-EM structure of EmrE provides the key to modeling its transmembrane domain.

The RND permease superfamily: an ancient, ubiquitous and diverse family that includes human disease and development proteins. A family of gram-negative bacterial outer membrane factors that function in the export of proteins, carbohydrates, drugs and heavy metals from gram-negative bacteria.

A family of extracytoplasmic proteins that allow transport of large molecules across the outer membranes of gram-negative bacteria. Zgurskaya HI, Nikaido H. Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli. AZ TFP Positive Thick. AZ 3DTM AZ 10XT. AZ 12XT. AZ 40XT. AZ IPS AZ P PL AZ nXT. AZ nLof Lift-off Resists. AZ E.

Anti-viral and immunomodulatory properties of new pro-glutathione GSH molecules. Curr Med Chem. Nakashima I. Redox-linked signal transduction pathways for protein tyrosine kinase activation. Antioxid Redox Signal. Nakamura H. Redox regulation of cellular activation. Ann Rev Immunol. Fowler A. World J Crit Care Med. Al Ghouleh I. Oxidases and peroxidases in cardiovascular and lung disease: new concepts in reactive oxygen species signaling.

Free Radic Biol Med. Huang K. J Med Virol. Chen L. Vera J. Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid. J Biol Chem. Carr A. Vitamin C and immune function. Bharara A. Intravenous vitamin C administered as adjunctive therapy for recurrent acute respiratory distress syndrome. Case Rep Crit Care. Kim Y. Immune Netw. Jariwalla R. Antiviral and immunomodulatory activities of ascorbic acid.

Subcell Biochem. Madhusudana S. In vitro inactivation of the rabies virus by ascorbic acid. Int J Infect Dis. Zarubaev V. Protective activity of ascorbic acid at influenza infection.

Infektsiia Immunitet. Wilson J. Evaluation of vitamin C for adjuvant sepsis therapy. Maggini S. Vitamins C, D and zinc: synergistic roles in immune function and infections. Vitam Miner.

Fisher B. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock? Chen Y. Mediators Inflamm. Hosakote Y. Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis.

Andrades M. Antioxidant treatment reverses organ failure in rat model of sepsis: role of antioxidant enzymes imbalance, neutrophil infiltration, and oxidative stress.

J Surg Res. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Syed A. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. Padayatty S. Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. Nathens A. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients.

Ann Surg. Vitamin C and community-acquired pneumonia. Patel V. Dietary antioxidants significantly attenuate hyperoxia-induced acute inflammatory lung injury by enhancing macrophage function via reducing the accumulation of airway HMGB1. Int J Mol Sci. Crimi E. The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: a prospective, randomized, double-blind, placebo-controlled trial.

Anesth Analg. Marik P. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before—after study.

Zabet M. J Res Pharm Pract. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. Ran L. Extra dose of vitamin C based on a daily supplementation shortens the common cold: a meta-analysis of 9 randomized controlled trials. Biomed Res Int. Sadat U. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials.

J Am Coll Cardiol. Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis. BMC Cardiovasc Disord. Marcial-Vega V.