Página 15 dos resultados de 1768 itens digitais encontrados em 0.051 segundos

Mycobacteriocidal Action of Exogenous Nitric Oxide

Long, Richard; Light, Bruce; Talbot, James A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/1999 EN
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We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (<100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.

Assessment of the Effect of Amphotericin B on the Vitality of Candida albicans

Liao, Robert S.; Rennie, Robert P.; Talbot, James A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/1999 EN
Relevância na Pesquisa
783.67695%
The processes involved in cell death are complex, and individual techniques measure specific fractions of the total population. The interaction of Candida albicans with amphotericin B was measured with fluorescent probes with different cellular affinities. These were used to provide qualitative and quantitative information of physiological parameters which contribute to fungal cell viability. SYBR Green I and 5,(6)-carboxyfluorescein were used to assess membrane integrity, and bis-(1,3-dibutylbarbituric acid)trimethine oxonol and 3,3-dihexyloxacarbocyanine iodide were used to evaluate alterations in membrane potential. The fluorescent indicators were compared with replication competency, the conventional indicator of viability. By using these tools, the evaluation of the response of C. albicans to amphotericin B time-kill curves delineated four categories which may represent a continuum between alive and dead. The data showed that replication competency (CFU per milliliter) as determined by conventional antifungal susceptibility techniques provided only an estimate of inhibition. Interpretation of fluorescent staining characteristics indicated that C. albicans cells which were replication incompetent after exposure to greater than 0.5 μg of amphotericin B per ml still maintained degrees of physiological function.

LY303366 Exhibits Rapid and Potent Fungicidal Activity in Flow Cytometric Assays of Yeast Viability

Green, Lisa J.; Marder, Philip; Mann, Larry L.; Chio, Li-Chun; Current, William L.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/1999 EN
Relevância na Pesquisa
783.235%
LY303366 is a semisynthetic analog of the antifungal lipopeptide echinocandin B that inhibits (1,3)-β-d-glucan synthase and exhibits efficacy in animal models of human fungal infections. In this study, we utilized flow cytometric analysis of propidium iodide uptake, single-cell sorting, and standard microbiological plating methods to study the antifungal effect of LY303366 on Saccharomyces cerevisiae and Candida albicans. Our data indicate that an initial 5-min pulse treatment with LY303366 caused yeasts to take up propidium iodide and lose their ability to grow. Amphotericin B and cilofungin required longer exposure periods (30 and 180 min, respectively) and higher concentrations to elicit these fungicidal effects. These two measurements of fungicidal activity by LY303366 were highly correlated (r > 0.99) in concentration response and time course experiments. As further validation, LY303366-treated yeasts that stained with propidium iodide were unable to grow in single-cell-sorted cultures. Our data indicate that LY303366 is potent and rapidly fungicidal for actively growing yeasts. The potency and rapid action of this new fungicidal compound suggest that LY303366 may be useful for antifungal therapy.

Effects of Enrofloxacin on Porcine Phagocytic Function

Schoevers, E. J.; van Leengoed, L. A. M. G.; Verheijden, J. H. M.; Niewold, T. A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/1999 EN
Relevância na Pesquisa
783.4353%
The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 μg/ml. Enrofloxacin (0.5 μg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5× the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida...

Structural and Functional Analysis of Horse Cathelicidin Peptides

Skerlavaj, Barbara; Scocchi, Marco; Gennaro, Renato; Risso, Angela; Zanetti, Margherita
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2001 EN
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783.6527%
Cathelicidin-derived antimicrobial peptides are a component of the peptide-based host defense of neutrophils and epithelia, with a widespread distribution in mammals. We recently reported the cDNA sequences of three putative horse myeloid cathelicidins, named eCATH-1, -2, and -3. A Western analysis was performed to investigate their presence in neutrophils and processing to mature peptides. eCATH-2 and eCATH-3, but not eCATH-1, were found to be present in uncleaved forms in horse neutrophils. The corresponding mature peptides were detected in inflammatory sites, suggesting that processing of the propeptides takes place upon neutrophil activation. A functional characterization was then performed with synthetic eCATH peptides. Circular dichroism measurements indicated an amphipathic α-helical conformation of these peptides in an anisotropic environment, and in vitro assays revealed a potent activity and a broad spectrum of antimicrobial activity for eCATH-1 and a somewhat more restricted spectrum of activity for eCATH-2. Conversely, a strong dependence on salt concentration was observed when the activity of eCATH-3 was tested. This peptide efficiently killed bacteria and some fungal species, i.e., Cryptococcus neoformans and Rhodotorula rubra...

Peptide Deformylase as an Antibacterial Drug Target: Assays for Detection of Its Inhibition in Escherichia coli Cell Homogenates and Intact Cells

Apfel, Christian M.; Evers, Stefan; Hubschwerlen, Christian; Pirson, Wolfgang; Page, Malcolm G. P.; Keck, Wolfgang
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2001 EN
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783.45234%
An assay was developed to determine the activity of peptide deformylase (PDF) inhibitors under conditions as close as possible to the physiological situation. The assay principle is the detection of N-terminal [35S]methionine labeling of a protein that contains no internal methionine. If PDF is active, the deformylation of the methionine renders the peptide a substrate for methionine aminopeptidase, resulting in the removal of the N-terminal methionine label. In the presence of a PDF inhibitor, the deformylation is blocked so that the N-formylated peptide is not processed and the label is detected. Using this assay, it is possible to determine the PDF activity under near-physiological conditions in a cell-free transcription-translation system as well as in intact bacterial cells.

ATP Synthase Is Necessary for Microcin H47 Antibiotic Action

Trujillo, Mónica; Rodríguez, Eliana; Laviña, Magela
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2001 EN
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783.07984%
Microcin H47 is a gene-encoded peptide antibiotic produced by a natural Escherichia coli strain isolated in Uruguay. In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed. These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action. The possibility that this last structure contains the antibiotic target is discussed.

A Novel Action of the Proton Pump Inhibitor Rabeprazole and Its Thioether Derivative against the Motility of Helicobacter pylori

Tsutsui, Nanako; Taneike, Ikue; Ohara, Tatsuki; Goshi, Satoshi; Kojio, Seiichi; Iwakura, Nobuhiro; Matsumaru, Hiroyuki; Wakisaka-Saito, Noriko; Zhang, Hui-Min; Yamamoto, Tatsuo
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2000 EN
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783.3749%
The motility of Helicobacter pylori was maximum at 37°C and at pH 6. A newly developed proton pump inhibitor, rabeprazole (RPZ), and its thioether derivative (RPZ-TH) markedly inhibited the motility of H. pylori. The concentrations of the drug necessary to inhibit 50% of the motility were 0.25, 16, 16, and >64 μg/ml for RPZ-TH, RPZ, lansoprazole, and omeprazole, respectively. No such inhibitory effects were observed with H2 blockers or anti-H. pylori agents. The motilities of Campylobacter jejuni and C. coli—but not those of Vibrio cholerae O1 and O139, Vibrio parahaemolyticus, Salmonella enterica serovar Typhimurium, and Proteus mirabilis—were also inhibited. Prolonged incubation with RPZ or RPZ-TH inhibited bacterial growth of only H. pylori, except for a turbid colony mutant. The results indicate that RPZ and RPZ-TH have a characteristic inhibitory effect against the motility of H. pylori (spiral-shaped bacteria), which is distinguished from that against bacterial growth.

Chemiosmotic Mechanism of Antimicrobial Activity of Ag+ in Vibrio cholerae

Dibrov, Pavel; Dzioba, Judith; Gosink, Khoosheh K.; Häse, Claudia C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2002 EN
Relevância na Pesquisa
783.235%
Although the antimicrobial effects of silver salts were noticed long ago, the molecular mechanism of the bactericidal action of Ag+ in low concentrations has not been elucidated. Here, we show that low concentrations of Ag+ induce a massive proton leakage through the Vibrio cholerae membrane, which results in complete deenergization and, with a high degree of probability, cell death.

Ergosterol Biosynthesis Inhibitors Become Fungicidal when Combined with Calcineurin Inhibitors against Candida albicans, Candida glabrata, and Candida krusei

Onyewu, Chiatogu; Blankenship, Jill R.; Del Poeta, Maurizio; Heitman, Joseph
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2003 EN
Relevância na Pesquisa
783.2908%
Azoles target the ergosterol biosynthetic enzyme lanosterol 14α-demethylase and are a widely applied class of antifungal agents because of their broad therapeutic window, wide spectrum of activity, and low toxicity. Unfortunately, azoles are generally fungistatic and resistance to fluconazole is emerging in several fungal pathogens. We recently established that the protein phosphatase calcineurin allows survival of Candida albicans during the membrane stress exerted by azoles. The calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506) are dramatically synergistic with azoles, resulting in potent fungicidal activity, and mutant strains lacking calcineurin are markedly hypersensitive to azoles. Here we establish that drugs targeting other enzymes in the ergosterol biosynthetic pathway (terbinafine and fenpropimorph) also exhibit dramatic synergistic antifungal activity against wild-type C. albicans when used in conjunction with CsA and FK506. Similarly, C. albicans mutant strains lacking calcineurin B are markedly hypersensitive to terbinafine and fenpropimorph. The FK506 binding protein FKBP12 is required for FK506 synergism with ergosterol biosynthesis inhibitors, and a calcineurin mutation that confers FK506 resistance abolishes drug synergism. Additionally...

Human Salivary Histatin 5 Fungicidal Action Does Not Induce Programmed Cell Death Pathways in Candida albicans

Wunder, David; Dong, Jin; Baev, Didi; Edgerton, Mira
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /01/2004 EN
Relevância na Pesquisa
783.4996%
Salivary histatins (Hsts) are potent candidacidal proteins that induce a nonlytic form of cell death in Candida albicans accompanied by loss of mean cell volume, cell cycle arrest, and elevation of intracellular levels of reactive oxygen species (ROS). Since these phenotypes are often markers of programmed cell death and apoptosis, we investigated whether other classical markers of apoptosis, including generation of intracellular ROS and protein carbonyl groups, chromosomal fragmentation (laddering), and cytochrome c release, are found in Hst 5-mediated cell death. Increased intracellular levels of ROS in C. albicans were detected in cells both following exogenous application of Hst 5 and following intracellular expression of Hst 5. However, Western blot analysis failed to detect specifically increased protein carbonylation in Hst 5-treated cells. There was no evidence of chromosomal laddering and no cytochrome c release was observed following treatment of C. albicans mitochondria with Hst 5. Superoxide dismutase enzymes of C. albicans and Saccharomyces cerevisiae provide essential protection against oxidative stress; therefore, we tested whether SOD mutants have increased susceptibility to Hst 5, as expected if ROS mediate fungicidal effects. Cell survival of S. cerevisiae SOD1/SOD2 mutants and C. albicans SOD1 mutants following Hst 5 treatment (31 μM) was indistinguishable from the survival of wild-type cells treated with Hst 5. We conclude that ROS may not play a direct role in fungicidal activity and that Hst 5 does not initiate apoptosis or programmed cell death pathways.

Genetic and Physiological Studies on the Site of Action of Distamycin A

Siccardi, A. G.; Lanza, E.; Nielsen, E.; Galizzi, A.; Mazza, G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1975 EN
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783.3366%
Two new genetic loci of Bacillus subtilis are identified by mutations that confer resistance to distamycin A and to other antibacterial agents. The chromosomal region where they map probably contains a cluster of genes whose products are related to membrane structure and function. Some of the biological effects of distamycin A are still in evidence in the resistant mutants indicating that the drug possibly acts at multiple sites. Most biological effects of the drug (including the phenotypic correction of a morphopoietic mutation) are likely to be due to the interaction of distamycin A with membrane (or surface) structures.

3-Aminooxy-1-Aminopropane and Derivatives Have an Antiproliferative Effect on Cultured Plasmodium falciparum by Decreasing Intracellular Polyamine Concentrations

Das Gupta, Robin; Krause-Ihle, Tanja; Bergmann, Bärbel; Müller, Ingrid B.; Khomutov, Alex R.; Müller, Sylke; Walter, Rolf D.; Lüersen, Kai
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2005 EN
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783.3749%
The intraerythrocytic development of Plasmodium falciparum correlates with increasing levels of the polyamines putrescine, spermidine, and spermine in the infected red blood cells; and compartmental analyses revealed that the majority is associated with the parasite. Since depletion of cellular polyamines is a promising strategy for inhibition of parasite proliferation, new inhibitors of polyamine biosynthesis were tested for their antimalarial activities. The ornithine decarboxylase (ODC) inhibitor 3-aminooxy-1-aminopropane (APA) and its derivatives CGP 52622A and CGP 54169A as well as the S-adenosylmethionine decarboxlyase (AdoMetDC) inhibitors CGP 40215A and CGP 48664A potently affected the bifunctional P. falciparum ODC-AdoMetDC, with Ki values in the low nanomolar and low micromolar ranges, respectively. Furthermore, the agents were examined for their in vitro plasmodicidal activities in 48-h incubation assays. APA, CGP 52622A, CGP 54169A, and CGP 40215A were the most effective, with 50% inhibitory concentrations below 3 μM. While the effects of the ODC inhibitors were completely abolished by the addition of putrescine, growth inhibition by the AdoMetDC inhibitor CGP 40215A could not be antagonized by putrescine or spermidine. Moreover...

Structural Correlates of Antibacterial and Membrane-Permeabilizing Activities in Acylpolyamines

Balakrishna, Rajalakshmi; Wood, Stewart J.; Nguyen, Thuan B.; Miller, Kelly A.; Suresh Kumar, E. V. K.; Datta, Apurba; David, Sunil A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2006 EN
Relevância na Pesquisa
783.5923%
A homologous series of mono- and bis-acyl polyamines with varying acyl chain lengths originally synthesized for the purpose of sequestering lipopolysaccharide were evaluated for antimicrobial activity to test the hypothesis that these bis-cationic amphipathic compounds may also bind to and permeabilize intact gram-negative bacterial membranes. Some compounds were found to possess significant antimicrobial activity, mediated via permeabilization of bacterial membranes. Structure-activity relationship studies revealed a strong dependence of the acyl chain length on antimicrobial potency and permeabilization activity. Homologated spermine, bis-acylated with C8 or C9 chains, was found to profoundly sensitize Escherichia coli to hydrophobic antibiotics such as rifampin. Nonspecific cytotoxicity is a potential drawback of these membranophilic compounds. However, the surface activity of these cationic amphipaths is strongly attenuated under physiological conditions via binding to serum albumin. Significant antibacterial activity is still retained in the presence of physiological concentrations of human serum albumin, suggesting that these compounds may serve as leads in the development of novel adjuncts to conventional antimicrobial chemotherapy.

Eosin B as a Novel Antimalarial Agent for Drug-Resistant Plasmodium falciparum†

Massimine, Kristen M.; McIntosh, Michael T.; Doan, Lanxuan T.; Atreya, Chloé E.; Gromer, Stephan; Sirawaraporn, Worachart; Elliott, David A.; Joiner, Keith A.; Schirmer, R. Heiner; Anderson, Karen S.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2006 EN
Relevância na Pesquisa
783.4596%
4′,5′-Dibromo-2′,7′-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits Toxoplasma gondii in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC50) of 180 μM. As a non-active-site inhibitor of the bifunctional T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on Plasmodium falciparum. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC50 of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall...

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans ▿ †

Brena, Sonia; Cabezas-Olcoz, Jonathan; Moragues, María D.; Fernández de Larrinoa, Iñigo; Domínguez, Angel; Quindós, Guillermo; Pontón, José
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2011 EN
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783.54484%
We have developed a monoclonal antibody (MAb), C7, that reacts with the Als3p and enolase present in the Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of MAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in the presence of a subinhibitory concentration of MAb C7 (12.5 μg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with MAb C7. Of these, 28 were found to be upregulated and 21 were found to be downregulated. The categories of upregulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the downregulated genes (8/21). Results were validated by real-time PCR. Since these effects resembled those found under iron-limited conditions, the activity of MAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking the TPK1 gene and, to a lesser extent, the TPK2 gene were less sensitive to the candidacidal effect of MAb C7. FeCl3 or hemin at concentrations of ≥7.8 μM reversed the candidacidal effect of MAb C7 on C. albicans in a concentration-dependent manner. The results presented in this study provide evidence that the candidacidal effect of MAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans.

The Aminoglycoside Antibiotic Kanamycin Damages DNA Bases in Escherichia coli: Caffeine Potentiates the DNA-Damaging Effects of Kanamycin while Suppressing Cell Killing by Ciprofloxacin in Escherichia coli and Bacillus anthracis

Kang, Tina Manzhu; Yuan, Jessica; Nguyen, Angelyn; Becket, Elinne; Yang, Hanjing; Miller, Jeffrey H.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2012 EN
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783.3366%
The distribution of mutants in the Keio collection of Escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. Strains lacking one of a number of glycosylases (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB, SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the strongest sensitivity among the glycosylase- or direct lesion removal-deficient strains. This perhaps suggests the involvement of ethenoadenine adducts, resulting from reactive oxygen species and lipid peroxidation, since AlkB removes this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V (Pol V), or components of double-strand break repair indicate that kanamycin results in damaged base pairs that need to be removed or replicated past in order to avoid double-strand breaks that saturate the cellular repair capacity. Caffeine enhances the sensitivities of these repair-deficient strains to kanamycin and neomycin. The gene knockout mutants that display increased sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate that caffeine blocks DNA replication...

Compensation of the Metabolic Costs of Antibiotic Resistance by Physiological Adaptation in Escherichia coli

Händel, Nadine; Schuurmans, J. Merijn; Brul, Stanley; ter Kuile, Benno H.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2013 EN
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783.7744%
Antibiotic resistance is often associated with metabolic costs. To investigate the metabolic consequences of antibiotic resistance, the genomic and transcriptomic profiles of an amoxicillin-resistant Escherichia coli strain and the wild type it was derived from were compared. A total of 125 amino acid substitutions and 7 mutations that were located <1,000 bp upstream of differentially expressed genes were found in resistant cells. However, broad induction and suppression of genes were observed when comparing the expression profiles of resistant and wild-type cells. Expression of genes involved in cell wall maintenance, DNA metabolic processes, cellular stress response, and respiration was most affected in resistant cells regardless of the absence or presence of amoxicillin. The SOS response was downregulated in resistant cells. The physiological effect of the acquisition of amoxicillin resistance in cells grown in chemostat cultures consisted of an initial increase in glucose consumption that was followed by an adaptation process. Furthermore, no difference in maintenance energy was observed between resistant and sensitive cells. In accordance with the transcriptomic profile, exposure of resistant cells to amoxicillin resulted in reduced salt and pH tolerance. Taken together...

Modulation of Alternaria infectoria Cell Wall Chitin and Glucan Synthesis by Cell Wall Synthase Inhibitors

Fernandes, Chantal; Anjos, Jorge; Walker, Louise A.; Silva, Branca M. A.; Cortes, Luísa; Mota, Marta; Munro, Carol A.; Gow, Neil A. R.; Gonçalves, Teresa
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2014 EN
Relevância na Pesquisa
783.4074%
The present work reports the effects of caspofungin, a β-1,3-glucan synthase inhibitor, and nikkomycin Z, an inhibitor of chitin synthases, on two strains of Alternaria infectoria, a melanized fungus involved in opportunistic human infections and respiratory allergies. One of the strains tested, IMF006, bore phenotypic traits that conferred advantages in resisting antifungal treatment. First, the resting cell wall chitin content was higher and in response to caspofungin, the chitin level remained constant. In the other strain, IMF001, the chitin content increased upon caspofungin treatment to values similar to basal IMF006 levels. Moreover, upon caspofungin treatment, the FKS1 gene was upregulated in IMF006 and downregulated in IMF001. In addition, the resting β-glucan content was also different in both strains, with higher levels in IMF001 than in IMF006. However, this did not provide any advantage with respect to echinocandin resistance. We identified eight different chitin synthase genes and studied relative gene expression when the fungus was exposed to the antifungals under study. In both strains, exposure to caspofungin and nikkomycin Z led to modulation of the expression of class V and VII chitin synthase genes, suggesting its importance in the robustness of A. infectoria. The pattern of A. infectoria phagocytosis and activation of murine macrophages by spores was not affected by caspofungin. Monotherapy with nikkomycin Z and caspofungin provided only fungistatic inhibition...

New Amphiphilic Neamine Derivatives Active against Resistant Pseudomonas aeruginosa and Their Interactions with Lipopolysaccharides

Sautrey, Guillaume; Zimmermann, Louis; Deleu, Magali; Delbar, Alicia; Souza Machado, Luiza; Jeannot, Katy; Van Bambeke, Françoise; Buyck, Julien M.; Decout, Jean-Luc; Mingeot-Leclercq, Marie-Paule
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2014 EN
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783.4996%
The development of novel antimicrobial agents is urgently required to curb the widespread emergence of multidrug-resistant bacteria like colistin-resistant Pseudomonas aeruginosa. We previously synthesized a series of amphiphilic neamine derivatives active against bacterial membranes, among which 3′,6-di-O-[(2″-naphthyl)propyl]neamine (3′,6-di2NP), 3′,6-di-O-[(2″-naphthyl)butyl]neamine (3′,6-di2NB), and 3′,6-di-O-nonylneamine (3′,6-diNn) showed high levels of activity and low levels of cytotoxicity (L. Zimmermann et al., J. Med. Chem. 56:7691–7705, 2013). We have now further characterized the activity of these derivatives against colistin-resistant P. aeruginosa and studied their mode of action; specifically, we characterized their ability to interact with lipopolysaccharide (LPS) and to alter the bacterial outer membrane (OM). The three amphiphilic neamine derivatives were active against clinical colistin-resistant strains (MICs, about 2 to 8 μg/ml), The most active one (3′,6-diNn) was bactericidal at its MIC and inhibited biofilm formation at 2-fold its MIC. They cooperatively bound to LPSs, increasing the outer membrane permeability. Grafting long and linear alkyl chains (nonyl) optimized binding to LPS and outer membrane permeabilization. The effects of amphiphilic neamine derivatives on LPS micelles suggest changes in the cross-bridging of lipopolysaccharides and disordering in the hydrophobic core of the micelles. The molecular shape of the 3′...