Presence Of Cephalosporins Research Articles

Pbp4 provides transpeptidase activity to the FtsW-PbpB peptidoglycan synthase to drive cephalosporin resistance in Enterococcus faecalis.

Enterococci exhibit intrinsic resistance to cephalosporins, mediated in part by the class B penicillin-binding protein (bPBP) Pbp4 that exhibits low reactivity toward cephalosporins and thus can continue crosslinking peptidoglycan despite exposure to cephalosporins. bPBPs partner with cognate SEDS (shape, elongation, division, and sporulation) glycosyltransferases to form the core catalytic complex of peptidoglycan synthases that synthesize peptidoglycan at discrete cellular locations, although the SEDS partner for Pbp4 is unknown. SEDS-bPBP peptidoglycan synthases of enterococci have not been studied, but some SEDS-bPBP pairs can be predicted based on sequence similarity. For example, FtsW (SEDS)-PbpB (bPBP) is predicted to form the catalytic core of the peptidoglycan synthase that functions at the division septum (the divisome). However, PbpB is readily inactivated by cephalosporins, raising the question-how could the FtsW-PbpB synthase continue functioning to enable growth in the presence of cephalosporins? In this work, we report that the FtsW-PbpB peptidoglycan synthase is required for cephalosporin resistance of Enterococcus faecalis, despite the fact that PbpB is inactivated by cephalosporins. Moreover, Pbp4 associates with the FtsW-PbpB synthase and the TPase activity of Pbp4 is required to enable growth in the presence of cephalosporins in an FtsW-PbpB-synthase-dependent manner. Overall, our results implicate a model in which Pbp4 directly interacts with the FtsW-PbpB peptidoglycan synthase to provide TPase activity during cephalosporin treatment, thereby maintaining the divisome SEDS-bPBP peptidoglycan synthase in a functional state competent to synthesize crosslinked peptidoglycan. These results suggest that two bPBPs coordinate within the FtsW-PbpB peptidoglycan synthase to drive cephalosporin resistance in E. faecalis.

The determination of cetirizine in the presence of cephalosporins through novel RP-HPLC method and application in human serum

The determination of cetirizine in the presence of cephalosporins through novel RP-HPLC method and application in human serum

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli

BackgroundThe issue of carbapenem resistance in E.coli is very concerning and it is speculated that cumulative effect of both primary resistance genes and secondary resistance genes that act as helper to the primary resistance genes are the reason behind their aggravation. Therefore, here we attempted to find the role of two secondary resistance genes (SRG) ccdB and repA2 in carbapenem resistance in E. coli (CRE). In this context influential genes belonging to secondary resistome that act as helper to the primary resistance genes like blaNDM and blaCTX-M in aggravating β-lactam resistance were selected from an earlier reported in silico study. Transcriptional expression of the selected genes in clinical isolates of E.coli that were discretely harboring blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7 and blaCTX-M-15 with and without carbapenem and cephalosporin stress (2 μg/ml) was determined by real time PCR. Cured mutants sets that were lacking (i) primary resistance genes, (ii) secondary resistance genes and (iii) both primary and secondary resistance genes were prepared by SDS treatment. These sets were then subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method.ResultsOut of the 21 genes reported in the in silico study, 2 genes viz.repA2 and ccdB were selected for transcriptional expression analysis. repA2, coding replication regulatory protein, was downregulated in response to carbapenems and cephalosporins. ccdB, coding for plasmid maintenance protein, was also downregulated in response to carbapenems except imipenem and cephalosporins. Following plasmid elimination assay increase in diameter of zone of inhibition under stress of both antibiotics was observed as compared to uncured control hinting at the reversion of antibiotic susceptibility by the-then resistant bacteria.ConclusionSRGs repA2 and ccdB help sustenance of blaNDM and blaCTX-M under carbapenem and cephalosporin stress.

Corrosion inhibition of carbon steel by three kinds of expired cephalosporins in 0.1 M H2SO4

It is difficult to avoid corrosion to carbon steel in acidic solutions, thus, in order to inhibit the corrosion of carbon steel during the acid pickling process, inhibitors must be added to the acid pickling solutions. In this work, the corrosion inhibition of carbon steel by three kinds of expired cephalosporins in 0.1 M H2SO4 was investigated by electrochemical, weight loss and scanning electron microscopy (SEM) methods. For the carbon steel electrode, the electrochemical results revealed that the current density was decreased, while, the charge-transfer resistance was increased in the presence of cephalosporins in 0.1 M H2SO4 corrosive solution. The weight loss results confirmed that the addition of cephalosporins decreased the corrosion rate of carbon steel. Further, the inhibition efficiency was increased with the increase in the concentration of cephalosporins. The SEM analysis of carbon steel surface was performed to confirm the effect of cephalosporins on the corrosion inhibition. The presented research demonstrated the efficient use of expired drugs for effective corrosion inhibition which could be applied to the industries at the large scale.

Using M. marinum T6PP as a Model for M. tuberculosis Inhibitor Design

Trehalose-6-phosphate phosphatase (T6PP) is a member of the haloalkanoic acid dehalogenase superfamily (HADSF) acting upon trehalose 6-phosphate, an intermediate in the pathway by which glucose 6-phosphate is converted to trehalose (1). The gene encoding T6PP, otsB, is conserved among bacterial pathogens, such as Mycobacterium tuberculosis, but absent in mammalian species. Bacterial pathogens of the Mycolata taxon utilize trehalose to synthesize cord factor, a mycolic acid-derived membrane glycolipid enabling toxicity, pathogenicity, and phagocyte survival (2). The otsB-knockout of M. tuberculosis precludes pathogen growth in vitro and virulence in a mouse model (2); thus, T6PP inhibitors are desired as therapeutics. Due to the 76% sequence identity between M. marinum and M. tuberculosis T6PP, our study investigates the molecular structure of T6PP from the model organism M. marinum in order to understand the binding determinants of the M. tuberculosis ortholog. Toward this goal, we have determined the unliganded structure of M. marinum to 1.97 □ resolution with a magnesium ion cofactor. The structure consists of 3 domains: the N-terminal, Rossmann-like core and cap domains. Like many other unliganded T6PP structures, the active site, located at cap-core interface, is exposed to solvent and is not in a conformation competent to bind substrate. However, comparison of the individual domains with M. tuberculosis T6PP results in an RMSD score of 0.64, 0.60, and 0.85 for the N-terminal, core and cap domains, respectively. We have measured the steady-state kinetic constants of M. marinum T6PP as kcat of 13 s−1 and a Km of 150 μM, which are comparable to those from the M. tuberculosis enzyme (kcat of 10 s−1 and Km of 500 μM) (3). Together these data confirm that the M. marinum enzyme is a model for structural and kinetic studies. To date, collaboration with The Scripps Research Institute facilitated the discovery of two T6PP inhibitors: clinically employed compounds Closantel and Cephalosporin C. We have determined a Ki for M. marinum T6PP of 39 μM in the presence of Cephalosporin C. Based on clinical data reporting the usage of the drug for tuberculosis therapy (4), we postulate that Cephalosporin C inhibits T6PP by preventing cord factor synthesis and thereby bacterial pathogenicity. In the future, we seek to determine the liganded structure of M. marinum T6PP with potential inhibitors bound. Support or Funding Information This work was funded by the Arnold and Mabel Beckman Foundation and Boston University Undergraduate Research Opportunities Program. Newly determined structure of M. marinum T6PP overlaid onto known structure of M. tuberculosis T6PP. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

New biological properties of tert-butyl cephalosporanate sulfones

tert-Butyl cephalosporanate 1,1-dioxides variously substituted in positions 7 and 3 were obtained from7-amino-deacetoxycephalosporanic acid (7-ADCA) and 7-aminocephalosporanic acid (7-ACA). It was found that the cephalosporins containing Aspirin and Diclofenac in a prodrug form in their 3-acyloxymethyl moiety release them after hydrolytic splitting of the β-lactam ring. They also demonstrated high efficacy as elastase inhibitors. Two of them stimulated the biosynthesis of nitric oxide in RAW 264.7 macrophages cells. The same effect observed in tumor and normal cells in the presence of cephalosporins was accompanied by cytotoxic effect in vitro.

Multiple antibiotic resistance (MAR) index and its reversion in Pseudomonas aeruginosa.

The MAR indexes of hospital isolates of Pseudomonas aeruginosa were determined with reference to nine different cephalosporins. The values for all the strains were higher than 0.2 suggesting their origin from a high risk source of contamination where antibiotics are often used. Emergence of MAR pathogenic strains of Ps. aeruginosa indicated possible nosocomial infection in the hospital environment. beta-Lactamases produced by these organisms were tested and their inhibition by clavulanic acid was studied. beta-Lactamase produced by one of these strains (Ps-1) could not be inhibited by clavulanic acid whereas beta-lactamases of three other strains (Ps-2, Ps-3 and Ps-4) could be inhibited by clavulanic acid in the presence of cephalosporins, suggesting a possible use of clavulanic acid in combination with cephalosporins, to combat beta-lactamase induced resistance in Ps. aeruginosa.

The synergistic action of cephalosporin C and benzylpenicillin against a penicillinase-producing strain of Staphylococcus aureus.

SUMMARY: Cephalosporin C, a hydrophilic, penicillin-like antibiotic which is insensitive to penicillinase, is much less active than benzylpenicillin against the Oxford strain of Staphylococcus aureus but much more active than benzylpenicillin against a penicillinase-producing strain of S. aurcus (D3R). When used together, cephalosporin C and benzylpenicillin act synergistically against S. aureus strain D3R in vitro, pzesumably because cephalosporin C is a competitive inhibitor of penicillinase. When grown under certain conditions in the presence of cephalosporin C. benzyl-penicillin, or bacitracin, the Oxford staphylococcus gives rise during a single culture to a resistant bacterial population consisting largely or partly of Gram-negative bacilli. In the presence of bacitracin a similar change also occurs with S. aureus strain D3R.