scholarly journals Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts

2015 ◽  
Vol 59 (7) ◽  
pp. 4148-4156 ◽  
Author(s):  
Yijia Li ◽  
Keith D. Green ◽  
Brooke R. Johnson ◽  
Sylvie Garneau-Tsodikova
Keyword(s):  
Inhibitory Effect ◽  
Culture Collection ◽  
Metal Salts ◽  
Common Mechanism ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Counter Ions ◽  
Large Repertoire

ABSTRACTAminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well asMycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+metal ions displayed an inhibitory effect on the resistance enzyme AAC(6′)-Ib inAcinetobacter baumanniiandEscherichia coli. In this study, we explore a wide array of metal salts (Mg2+, Cr3+, Cr6+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Au3+with different counter ions) and their inhibitory effect on a large repertoire of AACs [AAC(2′)-Ic, AAC(3)-Ia, AAC(3)-Ib, AAC(3)-IV, AAC(6′)-Ib′, AAC(6′)-Ie, AAC(6′)-IId, and Eis]. In addition, we determine the MIC values for amikacin and tobramycin in combination with a zinc pyrithione complex in clinical isolates of various bacterial strains (two strains ofA. baumannii, three ofEnterobacter cloacae, and four ofKlebsiella pneumoniae) and one representative of each species purchased from the American Type Culture Collection.

scholarly journals Evolution and Sequence Diversity of FhuA inSalmonellaandEscherichia

2018 ◽  
Vol 86 (11) ◽  
Author(s):  
Yejun Wang ◽  
Xiongbin Chen ◽  
Yueming Hu ◽  
Guoqiang Zhu ◽  
Aaron P. White ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Comparative Sequence Analysis ◽  
Sequence Diversity ◽  
Bacterial Cells ◽  
Bacterial Survival ◽  
Bacterial Strains ◽  
Content Type ◽  
High Conservation ◽  
High Selection ◽  
Clustering Pattern

ABSTRACTThefhuACDBoperon, present in a number ofEnterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as a transporter for physiologically important chelated ferric iron but also as a receptor for various bacteriophages, toxins, and antibiotics, which are pathogenic to bacterial cells. In this research,fhuAgene distribution and sequence diversity were investigated inEnterobacteriaceae, especiallySalmonellaandEscherichia. Comparative sequence analysis resulted in afhuAphylogenetic tree that did not match the expected phylogeny of species or trees of thefhuCDBgenes. ThefhuAsequences showed a unique mosaic clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins inSalmonellaandEscherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions/deletions and two substitution fragments were discovered, for which the combination of polymorphism patterns could well classify the different clusters. Structural modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops present as part of the FhuA external pocket. These frequently mutated regions are likely under high selection pressure, with bacterial strains balancing escape from phage infection or toxin/antibiotics attack viafhuAgene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusualfhuAclustering suggests that high-frequency exchange offhuAgenes has occurred between enterobacterial strains after distinctive species were established.

scholarly journals A Matter of Timing: Contrasting Effects of Hydrogen Sulfide on Oxidative Stress Response in Shewanella oneidensis

2015 ◽  
Vol 197 (22) ◽  
pp. 3563-3572 ◽  
Author(s):  
Genfu Wu ◽  
Fen Wan ◽  
Huihui Fu ◽  
Ning Li ◽  
Haichun Gao
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Shewanella Oneidensis ◽  
Inhibitory Effect ◽  
Time Dependent ◽  
Bacterial Cells ◽  
Bacterial Survival ◽  
Intracellular Iron ◽  
Content Type ◽  
Stress Responding

ABSTRACTHydrogen sulfide (H2S), well known for its toxic properties, has recently become a research focus in bacteria, in part because it has been found to prevent oxidative stress caused by treatment with some antibiotics. H2S has the ability to scavenge reactive oxygen species (ROS), thus preventing oxidative stress, but it is also toxic, leading to conflicting reports of its effects in different organisms. Here, withShewanella oneidensisas a model, we report that the effects of H2S on the response to oxidative stress are time dependent. When added simultaneously with H2O2, H2S promoted H2O2toxicity by inactivating catalase, KatB, a heme-containing enzyme involved in H2O2degradation. Such an inhibitory effect may apply to other heme-containing proteins, such as cytochromecbb3oxidase. When H2O2was supplied 20 min or later after the addition of H2S, the oxidative-stress-responding regulator OxyR was activated, resulting in increased resistance to H2O2. The activation of OxyR was likely triggered by the influx of iron, a response to lowered intracellular iron due to the iron-sequestering property of H2S. Given thatShewanellabacteria thrive in redox-stratified environments that have abundant sulfur and iron species, our results imply that H2S is more important for bacterial survival in such environmental niches than previously believed.IMPORTANCEPrevious studies have demonstrated that H2S is either detrimental or beneficial to bacterial cells. While it can act as a growth-inhibiting molecule by damaging DNA and denaturing proteins, it helps cells to combat oxidative stress. Here we report that H2S indeed has these contrasting biological functions and that its effects are time dependent. Immediately after H2S treatment, there is growth inhibition due to damage of heme-containing proteins, at least to catalase and cytochromecoxidase. In contrast, when added a certain time later, H2S confers an enhanced ability to combat oxidative stress by activating the H2O2-responding regulator OxyR. Our data reconcile conflicting observations about the functions of H2S.

scholarly journals The Broad-Spectrum Antiviral Compound ST-669 Restricts Chlamydial Inclusion Development and Bacterial Growth and Localizes to Host Cell Lipid Droplets within Treated Cells

2014 ◽  
Vol 58 (7) ◽  
pp. 3860-3866 ◽  
Author(s):  
Kelsi M. Sandoz ◽  
William G. Valiant ◽  
Steven G. Eriksen ◽  
Dennis E. Hruby ◽  
Robert D. Allen ◽  
...  
Keyword(s):  
Host Cell ◽  
Broad Spectrum ◽  
Lipid Droplets ◽  
Microscopic Analysis ◽  
Inhibitory Effect ◽  
Common Mechanism ◽  
Dependent Manner ◽  
Antiviral Compound ◽  
Content Type ◽  
Cell Lipid

ABSTRACTNovel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacteriumCoxiella burnetiiin Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetiiactivity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process.

scholarly journals Affectivity of Zatoria multiflora Boiss extracts Against Bacteria

2011 ◽  
Vol 46 (1) ◽  
pp. 105-110
Author(s):  
M Ur Rahman ◽  
S Gul ◽  
EA Odhano ◽  
Ir Hafeez ◽  
RB Tareen
Keyword(s):  
Staphylococcus Aureus ◽  
Methanol Extract ◽  
Inhibitory Effect ◽  
Bacterial Strains ◽  
It Use ◽  
Gram Positive ◽  
Reference Drug ◽  
Gram Negative ◽  
Bacterial Diseases ◽  
Gram Positive Bacteria

The extracts of Zatoria multiflora Boiss were evaluated for prospective antibacterial activity against gram negative and gram positive bacteria. Cefoperazone is used as antibacterial reference drug. The activity of ethanol and methanol extract varied from organism to organism. The inhibitory effect of both the extracts and their 50/50 combination was more pronounced against gram positive bacteria. The MIC and MBC values were in the range of 1.718-6.25 and 2.832-6.25 mg/ml respectively. Significant (p=0.05) synergistic effect of combination of EtOH and MeOH extracts was recorded against Staphylococcus aureus ATCC 29213, Staphylococcus aureus ATCC 25923 while additive effect against rest of the bacterial strains. The present studies provide evidences for presence of antibacterial elements in alcoholic extracts and recommends for more exploration for it use against bacterial diseases. Key words: Extracts; Zatoria multiflora Boiss; Antibacterial; MIC; MBC; Synergistic. DOI: http://dx.doi.org/10.3329/bjsir.v46i1.3652 Bangladesh J. Sci. Ind. Res. 46(1), 105-110, 2011

scholarly journals Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-ResistantPseudomonas aeruginosaInfection

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Hee Kyoung Kang ◽  
Chang Ho Seo ◽  
Tudor Luchian ◽  
Yoonkyung Park
Keyword(s):  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Helical Structure ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACTPseudin-2, isolated from the frogPseudis paradoxa, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable antimicrobial peptides (AMPs), we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. In addition, truncated analogs of pseudin-2 and Lys-substituted peptides were synthesized to produce linear 18-residue amphipathic α-helices, which were further investigated for their mechanism and functions. These truncated analogs exhibited higher antimicrobial activity and lower cytotoxicity than pseudin-2. In particular, Pse-T2 showed marked pore formation, permeabilization of the outer/inner bacterial membranes, and DNA binding. Fluorescence spectroscopy and scanning electron microscopy showed that Pse-T2 kills bacterial cells by disrupting membrane integrity.In vivo, wounds infected with multidrug-resistant (MDR)Pseudomonas aeruginosahealed significantly faster when treated with Pse-T2 than did untreated wounds or wounds treated with ciprofloxacin. Moreover, Pse-T2 facilitated infected-wound closure by reducing inflammation through suppression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α). These data suggest that the small antimicrobial peptide Pse-T2 could be useful for future development of therapeutic agents effective against MDR bacterial strains.

scholarly journals Abundant Extractable Metabolites from Temperate Tree Barks: The Specific Antimicrobial Activity of Prunus Avium Extracts

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 111 ◽  
Author(s):  
Amin Abedini ◽  
Marius Colin ◽  
Jane Hubert ◽  
Emilie Charpentier ◽  
Apostolis Angelis ◽  
...  
Keyword(s):  
Prunus Avium ◽  
Lethal Effect ◽  
Antimicrobial Activities ◽  
Inhibitory Effect ◽  
Major Constituent ◽  
Bacterial Strains ◽  
Gram Positive Bacteria ◽  
Tree Barks ◽  
13C Nuclear Magnetic Resonance

Tree barks are mainly considered as wood wastes from forestry activities, but represent valuable resources as they may contain antimicrobial compounds. Here, we aimed to evaluate the possible antimicrobial activities of bark extracts and to characterize the chemical composition of the most active extract. Ten methanol bark extracts were tested in vitro against 17 bacterial strains and 5 yeast strains, through minimum inhibitory concentration (MIC) and minimum bactericidal (or fungicidal) concentration (MBC/MFC) assays. The extract from Prunus avium (E2-4) displayed the largest bactericidal activity against Gram-positive bacteria, with a lethal effect on 6 out of 8 strains. Antibiofilm assays of E2-4 were performed by crystal violet staining and enumeration of adhered bacteria. Assays demonstrated a biofilm inhibitory effect of E2-4 against Staphylococcus aureus CIP 53.154 at concentrations equal to or higher than 250 µg/mL. Chemical profiling of E2-4 by 13C nuclear magnetic resonance (NMR) revealed the presence of dihydrowogonin as a major constituent of the extract. E2-4 was fractionated by centrifugal partition chromatography and the three fractions containing dihydrowogonin were tested for their antibacterial and antibiofilm activities, revealing similar activities to those of E2-4. Dihydrowogonin was positively assessed as an interesting antimicrobial compound, which could be valued from wastes of Prunus avium barks.

scholarly journals Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 489
Author(s):  
Julia A. Pavlova ◽  
Zimfira Z. Khairullina ◽  
Andrey G. Tereshchenkov ◽  
Pavel A. Nazarov ◽  
Dmitrii A. Lukianov ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Bacterial Strains ◽  
Translation Process ◽  
Gram Positive Bacteria ◽  
Alkyl Groups ◽  
Biochemical Assays ◽  
Bacterial Ribosome ◽  
Derivatives Of

In the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP in bacterial ribosomes differs from that of CHL. By simulating the dynamics of CAM-Cn-TPP complexes with bacterial ribosomes, we proposed a possible explanation for the specificity of the action of these analogs in the translation process. CAM-C10-TPP and CAM-C14-TPP more strongly inhibit the growth of the Gram-positive bacteria, as compared to CHL, and suppress some CHL-resistant bacterial strains. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds targeting both the ribosomes and cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds has an inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells possess qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.

scholarly journals In vitro biological activity of liposomal-containing antimony trioxide

2021 ◽  
Vol 10 (11) ◽  
pp. e391101119755
Author(s):  
Altevir Rossato Viana ◽  
Angelita Bottega ◽  
Marissa Bolson Serafin ◽  
Bruno Salles ◽  
Rosmari Horner ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Lines ◽  
Ph Value ◽  
Culture Collection ◽  
Free Form ◽  
Antimony Trioxide ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Diphenyltetrazolium Bromide

Antimonials are used as chemotherapy for leishmaniasis, but have limited results due to their toxicity and broad resistance already acquired by the parasites. Nanotechnology offers an alternative to reduce these effects through the use of biocompatible nanocarriers, which can be vectorized to the target site. In addition, the redirection of molecules, already developed for the treatment of other pathologies, has the advantage of being already approved for therapy by regulatory agencies. The present study addresses the production of liposomal vesicles containing antimony trioxide (LC Sb2O3), as well as the evaluation of activity against tumor and bacterial cells. We produce liposomes in order of nanometric size, polydispersity index (PDI <0.3), pH value close to physiological (7.2), and zeta potential (anionic). Cytotoxicity was evaluated in 24 and 72 hours, in the HepG2, T98G, and U87MG tumor cell lines, by the method (3-4.5 dimethylthiazole-2.5 diphenyltetrazolium bromide) (MTT). The minimum inhibitory concentration (MIC) was tested on three bacterial strains (American Type Culture Collection – ATCC-Escherichia coli ATCC 35218, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and mandatory (Staphylococcus aureus and Klebsiella pneumoniae). The liposomes were more cytotoxic than Sb2O3 in the free form, for all tested cell lines. This effect was stronger after 72 hours incubation. Antimony trioxide in both free and liposomal forms showed low antibacterial activity. Based on our results, we suggest that liposomes containing antimony trioxide have the potential for the repositioning of drugs addressing anticancer therapy.

scholarly journals Sulfide ProtectsStaphylococcus aureusfrom Aminoglycoside Antibiotics but Cannot Be Regarded as a General Defense Mechanism against Antibiotics

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Julia Weikum ◽  
Niklas Ritzmann ◽  
Nils Jelden ◽  
Anna Klöckner ◽  
Sebastian Herkersdorf ◽  
...  
Keyword(s):  
Defense Mechanism ◽  
Model Organism ◽  
Inhibitory Effect ◽  
Aminoglycoside Antibiotics ◽  
Drug Uptake ◽  
Protective Mechanism ◽  
Bacterial Cells ◽  
Content Type ◽  
Sulfide Production ◽  
The Impact

ABSTRACTSulfide production has been proposed to be a universal defense mechanism against antibiotics in bacteria (K. Shatalin, E. Shatalina, A. Mironov, and E. Nudler, Science 334:986–990, 2011, doi:10.1126/science.1209855). To gain insight into the mechanism underlying sulfide protection, we systematically and comparatively addressed the interference of sulfide with antibiotic activity againstStaphylococcus aureus, as a model organism. The impact of sulfide and sulfide precursors on the antibiotic susceptibility ofS. aureusto the most important classes of antibiotics was analyzed using modified disk diffusion assays, killing kinetic assays, and drug uptake studies. In addition, sulfide production and the impact of exogenously added sulfide on the physiology ofS. aureuswere analyzed. Sulfide protection was found to be limited to aminoglycoside antibiotics, which are known to be taken up by bacterial cells in an energy-dependent process. The protective mechanism was found to rely on an inhibitory effect of sulfide on the bacterial respiratory chain, leading to reduced drug uptake.S. aureuswas found to be incapable of producing substantial amounts of sulfide. We propose that bacterial sulfide production should not be regarded as a general defense mechanism against antibiotics, since (i) it is limited to aminoglycosides and (ii) production levels vary considerably among species and, as forS. aureus, may be too low for protection.

scholarly journals Mobile Genetic Elements Associated with Antimicrobial Resistance

2018 ◽  
Vol 31 (4) ◽  
Author(s):  
Sally R. Partridge ◽  
Stephen M. Kwong ◽  
Neville Firth ◽  
Slade O. Jensen
Keyword(s):  
Mobile Genetic Elements ◽  
Bacterial Cells ◽  
Gram Positive ◽  
Bacterial Gene ◽  
Major Health ◽  
Gram Negative ◽  
Content Type ◽  
Genetic Elements ◽  
Gram Positive Bacteria ◽  
Integrative Conjugative Elements

SUMMARYStrains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Enterobacterspp., andEscherichia coli), which have become the most problematic hospital pathogens.

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