scholarly journals The structure of alanine racemase fromAcinetobacter baumannii

2014 ◽  
Vol 70 (9) ◽  
pp. 1199-1205 ◽  
Author(s):  
Emily Davis ◽  
Emma Scaletti-Hutchinson ◽  
Helen Opel-Reading ◽  
Yoshio Nakatani ◽  
Kurt L. Krause

Acinetobacter baumanniiis an opportunistic Gram-negative bacterium which is a common cause of hospital-acquired infections. Numerous antibiotic-resistant strains exist, emphasizing the need for the development of new antimicrobials. Alanine racemase (Alr) is a pyridoxal 5′-phosphate dependent enzyme that is responsible for racemization between enantiomers of alanine. As D-alanine is an essential component of the bacterial cell wall, its inhibition is lethal to prokaryotes, making it an excellent antibiotic drug target. The crystal structure ofA. baumanniialanine racemase (AlrAba) from the highly antibiotic-resistant NCTC13302 strain has been solved to 1.9 Å resolution. Comparison of AlrAbawith alanine racemases from closely related bacteria demonstrates a conserved overall fold. The substrate entryway and active site of the enzymes were shown to be highly conserved. The structure of AlrAbawill provide the template required for future structure-based drug-design studies.

2019 ◽  
Vol 1 (2) ◽  
pp. 18-22
Author(s):  
O A Nazarchuk ◽  
V I Nahaichuk

Introduction. Non-fermenting Gram-negative bacilli are known as one of the most frequent causative agents of hospital-acquired infections. Acinetobacter baumannii, as causative agent of infection complications of different localization, has obtained recently high resistance to anti-biotics and has belonged to ESKAPE group of pathogens. Antimicrobials, recommended for the prophylaxis and therapy of hospital-acquired infections, have been failing in their effectiveness and lead to selection of antibiotic resistant strains of A. baumannii. The aim of this research was to substantiate the way of overcoming of resistance in clinical strains of A. baumannii, by means of synergic antimicrobial activity of antibiotics and antiseptic decamethoxinum®. Material and methods. The research was carried out on 190 clinical strains of A. baumannii, isolated from patients with burn disease during the period 2011–2015. The sensitivity of clinical strains of A. baumannii was determined to such antibiotics as ampicillin/sulbactam, cefoperazone, cefoperazone/sulbactam, meropenem, imipenem, amikacin, ciprofloxacin, gatifloxacin and antiseptic decamethoxinum® (DCM; Registration certificate No UA/14444/01/01 since 24.06.2015. Order of the Ministry of Health of Ukraine No 373). The sensitivity of A. baumannii to antibiotics and DCM was determined by means of disk diffusion test and serial dilution (Order of the Ministry of Health of Ukraine No167 since 05.04.2007; EUCAST expert rules).The study of the influence of antiseptic DCM on the sensitivity of acinetobacteria to antibiotics was studied on 35 clinical strains of A. baumannii, drafted from the general number of isolates enrolled in the research. For this, the sensitivity of A. baumannii to antibiotics in the presence of sub-minimal inhibitory concentrations (subMIC) of DCM was identified. The received experimental data were analyzed by “Statistica 6.0”. Results and discussion. The changes of antibiotic sensitivity profile of A. baumannii for five years were shown. It was found that the sensitivity of A. baumannii to majority of antibiotics, selected for study, decreased significantly. But the only ampicillin/sulbactam was found to have vice versa tendency. We found the rising quantity of antibiotic resistant strains of A. baumannii. At the same time, high resistance of acinetobacteria to fluoroquinolones (ciprofloxacin– 96,1%; gatifloxacin– 95,8%) was found in 2015. The in vitro research of combined activity of DCM antiseptic remedy and early mentioned antibiotics against clinical strains of A. baumannii demonstrated the reveal antibiotic effectiveness. As follows, minimal inhibitory concentrations of antibiotics decreased in 1.5–4 times in the mediums which contained subMIC of DCM. Especially this tendency was found in resistant clinical strains. Conclusion. Under selective influence of antibiotics protected by β-lactamase inhibitors, carbapenems, fluoroquinolones aminoglycosides increase the antibiotic resistance in A. baumannii, causative agents of infectious complications in patients with burn disease. The antiseptic remedy decamethoxinum® helps to improve antibiotic sensitivity in resistant A. baumannii.


Medicine ◽  
2016 ◽  
Vol 95 (27) ◽  
pp. e4099 ◽  
Author(s):  
Ngai Kien Le ◽  
Wertheim HF ◽  
Phu Dinh Vu ◽  
Dung Thi Khanh Khu ◽  
Hai Thanh Le ◽  
...  

2005 ◽  
Vol 28 (11) ◽  
pp. 1157-1162 ◽  
Author(s):  
J.M. Patti

Nosocomial or hospital-acquired infections are associated with prolonged hospitalizations and increased healthcare costs. Infections associated with surgical implants are becoming more difficult and more costly to manage, as they require repeated surgical procedures and a longer period of time to treat patients. Continued advances in the use of medical devices, an increase in the number of immunocompromised patients, and a steady rise in the prevalence of antibiotic-resistant organisms has renewed interest in the development of novel therapies that can be used to prevent and treat nosocomial infections. This review provides an overview of bacterial adhesins and focuses on novel immunological therapies developed to treat staphylococcal infections.


Author(s):  
Fernanda Silva dos Santos ◽  
Luiz Affonso de Paula Junior ◽  
Gabriel Farias Araujo ◽  
Wellington Thadeu de Alcantara Azevedo ◽  
Steven Dutt Ross ◽  
...  

Fecal enterococci are generally not virulent; however, multidrug-resistant strains have emerged as leading causes of hospital-acquired infections. Thus, periodic enterococci monitoring should be included in highly populated cities to control the dissemination of multidrug-resistant strains to the marine environment. This study aimed to quantify enterococci bacteria from water and intertidal sediment samples in a beach located near Rio de Janeiro touristic spots. We also intended to accomplish if enterococci should be included in touristic beaches sanitary monitoring. Toward this approach, we monitored from August to December 2014 fecal indicator bacteria (FIB) at a beach close to some touristic spots through multiple tube method. Although FIB quantification was within sanitary standards of Brazilian legislation, high enterococci densities (=30 MNP.100 mL-1) were detected in the water collected in August. Thus, enterococci monitoring should be included in touristic beaches to avoid the risk of multidrug-resistant bacteria dissemination among swimmers and beachgoers.


2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Brock A. Arivett ◽  
Dave C. Ream ◽  
Steven E. Fiester ◽  
Destaalem Kidane ◽  
Luis A. Actis

Pseudomonas aeruginosa , a Gram-negative bacterium that causes severe hospital-acquired infections, is grouped as an ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species) pathogen because of its extensive drug resistance phenotypes and effects on human health worldwide. Five multidrug resistant P. aeruginosa strains isolated from wounded military personnel were sequenced and annotated in this work.


2020 ◽  
Vol 11 ◽  
Author(s):  
Belinda Loh ◽  
Jiayuan Chen ◽  
Prasanth Manohar ◽  
Yunsong Yu ◽  
Xiaoting Hua ◽  
...  

Acinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analyzed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analyzed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined to be approximately 4 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analyzed the existence of genes that are encoded in the prophages, which may confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.


2019 ◽  
Vol 15 (2) ◽  
pp. 91-102
Author(s):  
Rosy Kumari ◽  
Ratish Chandra Mishra ◽  
Shivani Yadav ◽  
Jaya Parkash Yadav

Background: Enterococcus faecalis has attracted much attention in recent times due to its increased virulence in hospital-acquired infections. Cardamom which is an exotic spice in food items can be proposed for its antimicrobial potential. In the present study, alanine racemase (AlaR) of the bacteria was considered as inhibitors’ target due to its crucial role in cell wall synthesis. Methods: GC-MS analysis of Cardamom extract was performed and the identified phytochemicals were docked against AlaR using AutoDock 4.0. Top score ligands were further subjected to Absorption, Distribution, Metabolism, Excretion (ADME) analysis. Results & Conclusion: Molecular docking studies reveal that among 85 phytoligands, ricinoleic acid, bombykol, 1,8- cineole, heptanoic acid, and linalool showed significant interaction to the enzyme with an energy of -7.81, -7.57, -7.03, -7.02 and -7 kcal/mol, respectively, as compared to its substrate (ΔG Alanine: -5.03 kcal/mol). Among all the five lead compounds, 1,8- cineole, heptanoic acid, and linalool exhibited high bioactivity score on druglikeliness. This enabled us to conclude that the compounds 1,8- cineole, heptanoic acid and linalool would be useful antibacterial agents against E. faecalis infections.


Author(s):  
Belinda Loh ◽  
Jiayuan Chen ◽  
Prasanth Manohar ◽  
Yunsong Yu ◽  
Xiaoting Hua ◽  
...  

AbstractAcinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analysed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analysed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined as 3.98 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analysed the existence of genes that are encoded in the prophages, which confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.


2021 ◽  
Vol 10 (48) ◽  
Author(s):  
Belinda Loh ◽  
Xiaoqing Wang ◽  
Xiaoting Hua ◽  
Junhan Luo ◽  
Tanye Wen ◽  
...  

Pseudomonas aeruginosa is a major public health concern, as drug-resistant strains increase mortality in hospital-acquired infections. We report the isolation and complete genome sequences of four lytic bacteriophages that target clinical multidrug-resistant P. aeruginosa strains.


2012 ◽  
Vol 61 (3) ◽  
pp. 153-160 ◽  
Author(s):  
IWONA GAWRYSZEWSKA ◽  
WALERIA HRYNIEWICZ ◽  
EWA SADOWY

Enterococcus faecalis plays a significant role in hospital-acquired infections (HAIs), and combination of penicillin with aminoglycoside is important in therapy of invasive HAIs. Penicillin resistance in this organism is due to modification of the drug target, penicillin-binding protein (PBP5), its overproduction and expression of β-lactamase. Although rare, this phenotype is often associated with multi-resistant high-risk enterococcal clonal complexes (HiRECCs), such as CC2 and CC9 which may promote its spread in the near future.


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