scholarly journals Transcriptomic analysis indicates the mode of action of the novel antibiotic MGB-BP-3 against Staphylococcus aureus

2019 ◽  
Vol 1 (1A) ◽  
Author(s):  
Leena Nieminen ◽  
Kimon Lemonidis ◽  
Douglas Browning ◽  
Iain Hunter ◽  
Colin Suckling ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mode Of Action ◽  
Transcriptomic Analysis ◽  
The Novel

scholarly journals The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

2015 ◽  
Vol 59 (11) ◽  
pp. 6844-6854 ◽  
Author(s):  
C. V. Garcia De Gonzalo ◽  
E. L. Denham ◽  
R. A. T. Mars ◽  
J. Stülke ◽  
W. A. van der Donk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Phosphotransferase System ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Distinct Mechanism ◽  
Genomic Studies ◽  
Increased Sensitivity ◽  
Bacterial Sensitivity

ABSTRACTThe mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) ofBacillusspecies as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such asBacillusspecies andStaphylococcus aureus, including methicillin-resistantS. aureus(MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin.

scholarly journals Mechanisms and Frequency of Resistance to Premafloxacin in Staphylococcus aureus: Novel Mutations Suggest Novel Drug-Target Interactions

2000 ◽  
Vol 44 (12) ◽  
pp. 3344-3350 ◽  
Author(s):  
Dilek Ince ◽  
David C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Fold Increase ◽  
Single Step ◽  
The Novel ◽  
Novel Mutations ◽  
Topoisomerase Iv ◽  
Double Mutation ◽  
Fourfold Increase ◽  
Novel Drug

ABSTRACT Premafloxacin is a novel 8-methoxy fluoroquinolone with enhanced activity against Staphylococcus aureus. We found premafloxacin to be 32-fold more active than ciprofloxacin against wild-type S. aureus. Single mutations in either subunit of topoisomerase IV caused a four- to eightfold increase in the MICs of both quinolones. A double mutation (gyrA and eithergrlA or grlB) caused a 32-fold increase in the MIC of premafloxacin, while the MIC of ciprofloxacin increased 128-fold. Premafloxacin appeared to be a poor substrate for NorA, with NorA overexpression causing an increase of twofold or less in the MIC of premafloxacin in comparison to a fourfold increase in the MIC of ciprofloxacin. The frequency of selection of resistant mutants was 6.4 × 10−10 to 4.0 × 10−7 at twofold the MIC of premafloxacin, 2 to 4 log10 less than that with ciprofloxacin. Single-step mutants could not be selected at higher concentrations of premafloxacin. In five single-step mutants, only one previously described uncommon mutation (Ala116Glu), and four novel mutations (Arg43Cys, Asp69Tyr, Ala176Thr, and Pro157Leu), three of which were outside the quinolone resistance-determining region (QRDR) were found. Genetic linkage studies, in which incross ofgrlA + and outcross of mutations were performed, showed a high correlation between the mutations and the resistance phenotypes, and allelic exchange experiments confirmed the role of the novel mutations in grlA in resistance. Our results suggest that although topoisomerase IV is the primary target of premafloxacin, premafloxacin appears to interact with topoisomerase IV in a manner different from that of other quinolones and that the range of the QRDR of grlA should be expanded.

Mode of action of the alpha toxin of Staphylococcus aureus

1970 ◽  
Vol 16 (1) ◽  
pp. 47-50 ◽  
Author(s):  
G. M. Wiseman ◽  
J. D. Caird
Keyword(s):  
Staphylococcus Aureus ◽  
Proteolytic Activity ◽  
Mode Of Action ◽  
Differential Sensitivity ◽  
Aureus Strain ◽  
Red Cell ◽  
Alpha Toxin ◽  
Reaction Products ◽  
Phenol Reagent

Rabbit erythrocytes treated with the alpha toxin of Staphylococcus aureus, strain "Wood-46", liberate substances which contain nitrogen, absorb at 280 mμ, and react with Folin phenol reagent. The susceptibility of different erythrocyte species to alpha toxin is correlated with (a) the quantity of reaction products released by toxin from the cells and (b) the degree of natural proteolytic activity possessed by the cells. Alpha toxin was, however, without effect upon albumin, fibrinogen, casein, and hemoglobin even when these proteins had been denatured with urea. In view of the evidence, it is suggested that the toxin is secreted by the Staphylococcus as an inactive protease which must be activated by another protease. The degree of activity of this protease in various red cell species would explain their differential sensitivity to alpha toxin.

scholarly journals Inhibition of Antibiotic Efflux in Bacteria by the Novel Multidrug Resistance Inhibitors Biricodar (VX-710) and Timcodar (VX-853)

2004 ◽  
Vol 48 (11) ◽  
pp. 4171-4176 ◽  
Author(s):  
Steve Mullin ◽  
Nagraj Mani ◽  
Trudy H. Grossman
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Antibiotic Activity ◽  
Multiple Drug ◽  
The Novel ◽  
Multidrug Efflux ◽  
New Class ◽  
Clinically Significant ◽  
Antibiotic Efflux

ABSTRACT Inhibitors of mammalian multidrug efflux, such as the plant alkaloid reserpine, are also active in potentiating antibiotic activity by inhibiting bacterial efflux. Based on this precedent, two novel mammalian multiple drug resistance inhibitors, biricodar (VX-710) and timcodar (VX-853), were evaluated for activity in a variety of bacteria. Both VX-710 and VX-853 potentiated the activity of ethidium bromide (EtBr), a model efflux substrate, against three clinically significant gram-positive pathogens: Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Similar to reserpine, VX-710 and VX-853 directly blocked EtBr efflux in S. aureus. Furthermore, these compounds were effective in lowering the MICs of several clinically used antibiotics, including fluoroquinolones, suggesting that VX-710 and VX-853 are representatives of a new class of bacterial efflux inhibitors with the potential for use in combination therapy.

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