scholarly journals Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli

RSC Advances ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 5936-5944 ◽  
Author(s):  
Juan Wang ◽  
Yang Li ◽  
Haizhong Yan ◽  
Juan Duan ◽  
Xihua Luo ◽  
...  

Bacteria containing blaNDM-1 gene are a growing threat to almost all clinically β-lactam antibiotics. A semi-rational screening of the inhibitors and antibiotics against the New Delhi metallo-β-lactamase 1 has been developed in this study.

2019 ◽  
Vol 70 (5) ◽  
pp. 1778-1783
Author(s):  
Andreea-Loredana Golli ◽  
Floarea Mimi Nitu ◽  
Maria Balasoiu ◽  
Marina Alina Lungu ◽  
Cristiana Cerasella Dragomirescu ◽  
...  

To determine the resistance pattern of bacterial pathogens involved in infections of the patients aged between 18-64 years, admitted in a ICU from a 1518-bed university-affiliated hospital. A retrospective study of bacterial pathogens was carried out on 351 patients aged between 18-64 years admitted to the ICU, from January to December 2017. In this study there were analysed 469 samples from 351 patients (18-64 years). A total of 566 bacterial isolates were obtained, of which 120 strains of Klebsiella spp. (35.39%%), followed by Nonfermenting Gram negative bacilli, other than Pseudomonas and Acinetobacter (NFB) (75- 22.12%), Acinetobacter spp. (53 - 15.63%), Pseudomonas aeruginosa and Proteus (51 - 15.04%), and Escherichia coli (49 - 14.45%). The most common isolates were from respiratory tract (394 isolates � 69.61%). High rates of MDR were found for Pseudomonas aeruginosa (64.70%), MRSA (62.65%) and Klebsiella spp. (53.33%), while almost all of the isolated NFB strains were MDR (97.33%). There was statistic difference between the drug resistance rate of Klebsiella and E. coli strains to ceftazidime and ceftriaxone (p[0.001), cefuroxime (p[0.01) and to cefepime (p[0.01). The study revealed an alarming pattern of antibiotic resistance in the majority of ICU isolates.


2012 ◽  
Vol 78 (13) ◽  
pp. 4677-4682 ◽  
Author(s):  
Charlotte Valat ◽  
Frédéric Auvray ◽  
Karine Forest ◽  
Véronique Métayer ◽  
Emilie Gay ◽  
...  

ABSTRACTIn line with recent reports of extended-spectrum beta-lactamases (ESBLs) inEscherichia coliisolates of highly virulent serotypes, such as O104:H4, we investigated the distribution of phylogroups (A, B1, B2, D) and virulence factor (VF)-encoding genes in 204 ESBL-producingE. coliisolates from diarrheic cattle. ESBL genes, VFs, and phylogroups were identified by PCR and a commercial DNA array (Alere, France). ESBL genes belonged mostly to the CTX-M-1 (65.7%) and CTX-M-9 (27.0%) groups, whereas those of the CTX-M-2 and TEM groups were much less represented (3.9% and 3.4%, respectively). One ESBL isolate wasstx1andeaepositive and belonged to a major enterohemorrhagicE. coli(EHEC) serotype (O111:H8). Two other isolates wereeaepositive butstxnegative; one of these had serotype O26:H11. ESBL isolates belonged mainly to phylogroup A (55.4%) and, to lesser extents, to phylogroups D (25.5%) and B1 (15.6%), whereas B2 strains were quasi-absent (1/204). The number of VFs was significantly higher in phylogroup B1 than in phylogroups A (P= 0.04) and D (P= 0.02). Almost all of the VFs detected were found in CTX-M-1 isolates, whereas only 64.3% and 33.3% of them were found in CTX-M-9 and CTX-M-2 isolates, respectively. These results indicated that the widespread dissemination of theblaCTX-Mgenes within theE. colipopulation from cattle still spared the subpopulation of EHEC/Shiga-toxigenicE. coli(STEC) isolates. In contrast to other reports on non-ESBL-producing isolates from domestic animals, B1 was not the main phylogroup identified. However, B1 was found to be the most virulent phylogroup, suggesting host-specific distribution of virulence determinants among phylogenetic groups.


2019 ◽  
Author(s):  
Oldřich Hudeček ◽  
Roberto Benoni ◽  
Martin Culka ◽  
Martin Hubálek ◽  
Lubomír Rulíšek ◽  
...  

Dinucleoside polyphosphates (NpnNs), discovered more than 50 years ago,1 are pleiotropic molecules present in almost all types of cells.2 It has been shown that their intracellular concentration can under stress conditions increase from the µM to mM range 2,3. However, the cellular roles and mechanisms of action of NpnNs are still speculative4,5. They have never been considered as part of the RNA, even though they have similar chemical structures as already known RNA caps, such as the nicotinamide adenine dinucleotide (NAD)6-8 and 7-methylguanylate cap9. Here, we show that both methylated and non-methylated Npn Ns serve as RNA caps in Escherichia coli (E. coli). NpnNs are excellent substrates for T7 and E. coli RNA polymerases (RNAP) and efficiently initiate transcription. Further, we demonstrate that the E. coli decapping enzyme RNA 5’ pyrophosphohydrolase (RppH) is able to remove the NpnNs-cap from the RNA. RppH was, however, not able to cleave the methylated forms of the NpnN-caps, suggesting that the methylation adds an additional layer to the RNA stability regulation. Our work introduces an original perspective on the chemical structure of RNA in prokaryotes and the function of RNA caps. This is the first evidence that small molecules like NpnNs can act in cells via their incorporation into RNA and influence the cellular metabolism.


1986 ◽  
Vol 164 (5) ◽  
pp. 1407-1421 ◽  
Author(s):  
J E Gabay ◽  
J M Heiple ◽  
Z A Cohn ◽  
C F Nathan

We examined the subcellular location of bactericidal factors (BF) in human neutrophils, using an efficient fractionation scheme. Nitrogen bomb cavitates of DIFP-treated PMN were centrifuged through discontinuous Percoll gradients, each fraction extracted with 0.05 M glycine, pH 2.0, and tested for the killing of Escherichia coli. greater than 90% of BF coisolated with the azurophil granules. After lysis of azurophils, 98% of azurophil-derived BF (ADBF) sedimented with the membrane. ADBF activity was solubilized from azurophil membrane with either acid or nonionic detergent (Triton X-100, Triton X-114). Bactericidal activity was linear with respect to protein concentration over the range 0.3-30 micrograms/ml. 0.1-0.3 microgram/ml ADBF killed 10(5) E. coli within 30 min at 37 degrees C. At 1.4 micrograms/ml, 50% of 2 X 10(5) bacteria were killed within 5 min. ADBF was effective between pH 5-8, with peak activity at pH 5.5. Glucose (20 mM), EDTA (1-25 mM), and physiologic concentrations of NaCl or KCl had little or no inhibitory effect on ADBF. ADBF killed both Gram-positive and Gram-negative virulent clinical isolates, including listeria, staphylococci, beta-hemolytic streptococci, and Pseudomonas aeruginosa. Thus, under these conditions of cell disruption, fractionation, extraction, and assay, almost all BF in human PMN appeared to be localized to the membrane of azurophilic granules as a highly potent, broad-spectrum, rapidly acting protein(s) effective in physiologic medium. Some of these properties appear to distinguish ADBF from previously described PMN bactericidal proteins.


2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Atsushi Iguchi ◽  
Hironobu Nishii ◽  
Kazuko Seto ◽  
Jiro Mitobe ◽  
Kenichi Lee ◽  
...  

ABSTRACT The O-serogrouping of pathogenic Escherichia coli is a standard method for subtyping strains for epidemiological studies and controls. O-serogroup diversification shows a strong association with the genetic diversity in some O-antigen biosynthesis gene clusters. Through genomic studies, in addition to the types of O-antigen biosynthesis gene clusters (Og-types) from conventional O-serogroup strains, a number of novel Og-types have been found in E. coli isolates. To assist outbreak investigations and surveillance of pathogenic E. coli at inspection institutes, in previous studies, we developed PCR methods that could determine almost all conventional O-serogroups and some novel Og-types. However, there are still many Og-types that may not be determined by simple genetic methods such as PCR. Thus, in the present study, we aimed to develop an additional Og-typing PCR system. Based on the novel Og-types, including OgN32, OgN33, and OgN34, presented in this study, we designed an additional 24 PCR primer pairs targeting 14 novel and 2 diversified E. coli Og-types and 8 Shigella-unique Og-types. Subsequently, we developed 5 new multiplex PCR sets consisting of 33 primers, including the aforementioned 24 primers and 9 primers reported in previous studies. The accuracy and specificity of the PCR system was validated using approximately 260 E. coli and Shigella O-serogroup and Og-type reference strains. The Og-typing PCR system reported here can determine a wide range of Og-types of E. coli and may help epidemiological studies, in addition to the surveillance of pathogenic E. coli.


1969 ◽  
Vol 114 (2) ◽  
pp. 429-435 ◽  
Author(s):  
David J. Pillinger ◽  
John Hay ◽  
Ernest Borek

1. The ability of chemically hypermethylated Escherichia coli B transfer RNA to accept 19 amino acids was studied and the results were compared with those obtained with a control sample of E. coli B transfer RNA incubated under similar conditions in the absence of methylating agent. 2. There is a marked decrease in the ability of the modified transfer RNA to accept amino acids in almost all instances. 3. The acceptance of cysteine appears to be unique in that it is enhanced in the hypermethylated transfer RNA. 4. More detailed studies on the kinetics of acceptance for six amino acids is presented, emphasizing the variation in response of the individual amino acids. 5. Increasing hypermethylation causes a progressive decrease in the amino acid acceptance. 6. The results are discussed in terms of methylation at functional sites within the transfer RNA and possible conformational alterations to the structure of the macromolecule.


mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Akanksha Nigam ◽  
Tamar Ziv ◽  
Adi Oron-Gottesman ◽  
Hanna Engelberg-Kulka

ABSTRACT Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. By that means, under stress, the induced MazF generates a stress-induced translation machinery (STM) composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we performed a proteomic analysis of all the E. coli stress-induced proteins that are mediated through the chromosomally borne mazF gene. We show that the mRNAs of almost all of them are characterized by the presence of an ACA site up to 100 nucleotides upstream of the AUG initiator. Therefore, under stressful conditions, induced MazF processes mRNAs that are translated by STM. Furthermore, the presence of the ACA sites far upstream (up to 100 nucleotides) of the AUG initiator may still permit translation by the canonical translation machinery. Thus, such dual-translation mechanisms enable the bacterium under stress also to prepare proteins for immediate functions while coming back to normal growth conditions. IMPORTANCE The stress response, the strategy that bacteria have developed in order to cope up with all kinds of adverse conditions, is so far understood at the level of transcription. Our previous findings of a uniquely modified stress-induced translation machinery (STM) generated in E. coli under stress by the endoribonucleolytic activity of the toxin MazF opens a new chapter in understanding microbial physiology under stress at the translational level. Here, we performed a proteomic analysis of all the E. coli stress-induced proteins that are mediated by chromosomally borne MazF through STM.


1960 ◽  
Vol 111 (5) ◽  
pp. 601-609 ◽  
Author(s):  
Harrison F. Wood ◽  
Sonia Anderle ◽  
Carolyn W. Hammond ◽  
C. Phillip Miller

Young adult rabbits (2 to 3 kg.) were subjected to a single total body exposure of x-radiation ranging from 50 to 1200 r and tested frequently for the presence of Cx-reactive protein in their blood. It usually appeared in two phases separated by an interval of several days. The primary phase occurred 24 to 48 hours after irradiation in almost all (92 of 97) rabbits exposed to 500 r or more and in 4 of 16 exposed to 300 r or less. The secondary phase occurred during the 2nd week in many of the rabbits irradiated with 900 r or more and in a few irradiated with 700 r. Autopsy cultures failed to demonstrate the presence of infection in rabbits which died or were sacrificed during the primary phase. Bacterial infection was demonstrated, however, in almost all (21 of 24) rabbits autopsied and cultured during the secondary phase. After the disappearance of the primary phase in rabbits exposed to 700 or 900 r, the secondary phase could be elicited by initiating bacterial infection. Within 6 to 24 hours after intravenous inoculation of E. coli, Cx-reactive protein reappeared in the blood and persisted until death or termination of the experiment. Reappearance of the protein also followed the intravenous injection of killed E. coli but it disappeared again 1 to 2 days later. The results indicate that the primary phase is elicited by radiation injury per se and the secondary phase by bacterial infection.


2011 ◽  
Vol 76 (12) ◽  
pp. 1597-1606 ◽  
Author(s):  
Nemanja Trisovic ◽  
Bojan Bozic ◽  
Ana Obradovic ◽  
Olgica Stefanovic ◽  
Snezana Markovic ◽  
...  

A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 ?M, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.


2014 ◽  
Vol 70 (1) ◽  
pp. 108-113 ◽  
Author(s):  
N. D. Miranda ◽  
E. L. Oliveira ◽  
G. H. R. Silva

The purpose of this research was to study the disinfection of sanitary effluent from constructed wetlands, evaluating the oxidation of organic matter, the formation of formaldehyde, as well as the efficiency of total coliforms and Escherichia coli inactivation. A constant flow of ozone was applied to the batch system in 5 and 10 mg.O3 L−1 doses with contact times of 5 and 10 min. This study revealed that the average values of formaldehyde formation ranged between 259.00 and 379.00 μg L−1, which means that the values are within World Health Organization recommended values. The total coliforms and E. coli showed complete inactivation in almost all tests. The dose of ozone 5 mg.O3 L−1 and contact time of 5 min were sufficient for a significant reduction of the concentration levels of pathogens in constructed wetlands effluent with similar characteristics, thus allowing for its agricultural reuse.


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