scholarly journals Cloning, Expression, and Purification of Nucleoside Diphosphate Kinase from Acinetobacter baumannii

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Juhi Sikarwar ◽  
Sanket Kaushik ◽  
Mau Sinha ◽  
Punit Kaur ◽  
Sujata Sharma ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Pathogenic Bacteria ◽  
Nucleoside Diphosphate Kinase ◽  
Nitrilotriacetic Acid ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Gene Encoding ◽  
Hospital Acquired ◽  
Important Enzyme

Acinetobacter baumannii is a multidrug resistant pathogenic bacteria associated with hospital acquired infections. This bacterium possesses a variety of resistance mechanisms which makes it more difficult to control the bacterium with conventional drugs, and, so far no effective drug treatment is available against it. Nucleoside diphosphate kinase is an important enzyme, which maintains the total nucleotide triphosphate pool inside the cell by the transfer of γ-phosphate from NTPs to NDPs. The role of nucleoside diphosphate kinase (Ndk) has also been observed in pathogenesis in other organisms. However, intensive studies are needed to decipher its other putative roles in Acinetobacter baumannii. In the present study, we have successfully cloned the gene encoding Ndk and achieved overexpression in bacterial host BL-21 (DE3). The overexpressed protein is further purified by nickel-nitrilotriacetic acid (Ni-NTA) chromatography.

scholarly journals Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1126
Author(s):  
George L. Daikos ◽  
Clóvis Arns da da Cunha ◽  
Gian Maria Rossolini ◽  
Gregory G. Stone ◽  
Nathalie Baillon-Plot ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Real World Data ◽  
Serious Infections ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

scholarly journals Cefiderocol Resistance in Acinetobacter baumannii: Roles of β-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Saquib Malik ◽  
Monica Kaminski ◽  
David Landman ◽  
John Quale
Keyword(s):  
Acinetobacter Baumannii ◽  
Binding Protein ◽  
Receptor Gene ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Penicillin Binding Protein ◽  
Gram Negative ◽  
Content Type ◽  
Siderophore Receptors

ABSTRACT Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cefiderocol resistance was associated with reduced expression of the siderophore receptor gene pirA. Mutations involving PBP3 may have contributed to resistance in one strain. Additional studies are needed to assess the role of other siderophore receptors.

scholarly journals Acinetobacter baumanniiInfection and IL-17 Mediated Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Zihe Yan ◽  
Junjun Yang ◽  
Renjing Hu ◽  
Xichi Hu ◽  
Kong Chen
Keyword(s):  
Immune Response ◽  
Acinetobacter Baumannii ◽  
Military Personnel ◽  
Potential Role ◽  
Multidrug Resistant ◽  
Interleukin 17 ◽  
Hospital Acquired Infections ◽  
Host Pathogen Interaction ◽  
Hospital Acquired

Acinetobacter baumanniiis a significant cause of severe hospital-acquired infections with a recent rise in multidrug-resistant infections involving traumatic wounds of military personnel. The interleukin-17 (IL-17) pathway is essential for neutrophil recruitment in response to a variety of pathogens, while the control ofA. baumanniiinfection is known to be dependent on neutrophils. This suggests that IL-17 may play an important role inA. baumanniiinfection; however, this has yet to be studied. Here, we summarize the recent advances in understanding the host-pathogen interaction ofA. baumanniiand propose a potential role of the IL-17 pathway in generating a protective immune response.

scholarly journals Colistin heteroresistance and the involvement of the PmrAB regulatory system in Acinetobacter baumannii

2018 ◽  
Author(s):  
Yannick Charretier ◽  
Seydina M. Diene ◽  
Damien Baud ◽  
Sonia Chatellier ◽  
Emmanuelle Santiago-Allexant ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Population Analysis ◽  
Regulatory System ◽  
Clinical Problem ◽  
Multidrug Resistant ◽  
Regulatory Pathway ◽  
Colistin Resistance ◽  
Bacterial Killing ◽  
One Step

AbstractMultidrug-resistant Acinetobacter baumannii infection has recently emerged as a worldwide clinical problem and colistin is increasingly being used as last resort therapy. Despite its favorable bacterial killing, resistance and heteroresistance to colistin have been described. Mutations in the PmrAB regulatory pathway have been already associated with colistin resistance whereas the mechanisms for heteroresistance remain largely unknown. The purpose of the present study is to investigate the role of PmrAB in laboratory-selected mutants representative of global epidemic strains. During brief colistin exposure, colistin resistant and colistin heteroresistant mutants were selected in a one-step strategy. Population Analysis Profiling (PAP) was performed to confirm the suspected phenotype. Upon withdrawal of selective pressure, compensatory mutations were evaluated in another one-step strategy. A trans-complementation assay was designed to delineate the involvement of the PmrAB regulatory system using qPCR and PAP. Mutations in the PmrAB regulatory pathway were associated with colistin resistance and colistin heteroresistance as well. The transcomplementation assay provides a proof for the role played by changes in the PmrAB regulatory pathway. The level of colistin resistance is correlated to the level of expression of pmrC. The resistance phenotype was partially restored since the complemented strain became heteroresistant. This report shows the role of different mutations in the PmrAB regulatory pathway and warns on the development of colistin heteroresistance that could be present but not easily detected with routine testing.

Genomic fitness profiling of Acinetobacter baumannii reveals modes of action for common biocides and mechanisms of biocide-antibiotic antagonism

2021 ◽  
Author(s):  
Liping Li ◽  
Francesca Short ◽  
Karl Hassan ◽  
Varsha Naidu ◽  
Alaska Pokhrel ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Tricarboxylic Acid Cycle ◽  
Insertion Site ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Cell Respiration ◽  
Community Environments ◽  
Intracellular Targets

Abstract Biocides, such as antiseptics and disinfectants, are used ubiquitously for hygiene in households and for life-saving infection control in hospitals. An increasing concern is that the widespread use of biocides may contribute to the emergence and spread of multidrug-resistant bacteria. We performed transposon directed insertion site sequencing (TraDIS) to identify genes and key cellular pathways of the multidrug resistant nosocomial pathogen Acinetobacter baumannii, that affect host fitness during exposure to a panel of ten structurally-diverse and clinically-relevant biocides: silver nitrate, benzalkonium, cetyltrimethylammonium bromide (CTAB), chlorhexidine, triclosan, chloroxylenol, polyvidone iodine, bleach, glutaraldehyde and ethanol. Multiple genes encoding proteins localised either in the cell envelope or in the cytoplasm were shown to affect biocide susceptibility. These proteins are involved in multiple processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, suggesting that these biocides may have intracellular targets in addition to their known effects on the cell envelope. Based on the importance of cell respiration genes for A. baumannii fitness on biocides, we proposed and confirmed that apart from triclosan, the other 9 biocides at sub-inhibitory concentration can dissipate the membrane potential and lead to A. baumannii tolerance to antibiotics that have intracellular targets. Our results support the concern that residual biocides in clinical or community environments can promote the development of antibiotic resistance in pathogenic bacteria.

scholarly journals Characterization of RelA in Acinetobacter baumannii

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
María Pérez-Varela ◽  
Aimee R. P. Tierney ◽  
Ju-Sim Kim ◽  
Andrés Vázquez-Torres ◽  
Philip Rather
Keyword(s):  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Cell Physiology ◽  
Content Type ◽  
Content Model ◽  
Transposon Insertion ◽  
Downstream Effectors

ABSTRACT In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (ΔrelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The ΔrelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the ΔrelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the ΔrelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the ΔrelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model. IMPORTANCE Acinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.

scholarly journals The Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc Limitation

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Laura E. Hesse ◽  
Zachery R. Lonergan ◽  
William N. Beavers ◽  
Eric P. Skaar
Keyword(s):  
Acinetobacter Baumannii ◽  
Defense Mechanisms ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Content Type ◽  
Nutritional Immunity ◽  
Essential Nutrient ◽  
Health Organization

ABSTRACT Acinetobacter baumannii is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. A. baumannii is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health Organization to declare A. baumannii a “Priority 1: Critical” pathogen, for which the development of novel antimicrobials is desperately needed. Zinc (Zn) is an essential nutrient that pathogenic bacteria, including A. baumannii, must acquire from their hosts in order to survive. Consequently, vertebrate hosts have defense mechanisms to sequester Zn from invading bacteria through a process known as nutritional immunity. Here, we describe a Zn uptake (Znu) system that enables A. baumannii to overcome this host-imposed Zn limitation. The Znu system consists of an inner membrane ABC transporter and an outer membrane TonB-dependent receptor. Strains of A. baumannii lacking any individual Znu component are unable to grow in Zn-starved conditions, including in the presence of the host nutritional immunity protein calprotectin. The Znu system contributes to Zn-limited growth by aiding directly in the uptake of Zn into A. baumannii cells and is important for pathogenesis in murine models of A. baumannii infection. These results demonstrate that the Znu system allows A. baumannii to subvert host nutritional immunity and acquire Zn during infection.

scholarly journals Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 148 ◽  
Author(s):  
Cuong Hoang Quoc ◽  
Thao Nguyen Thi Phuong ◽  
Hai Nguyen Duc ◽  
Trung Tran Le ◽  
Hang Tran Thi Thu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Demographic Data ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Background: Acinetobacter baumannii (Ab) is an opportunistic bacterial pathogen found in hospital-acquired infections including nosocomial pneumonia, especially multidrug-resistant Ab. This study aims to survey the drug resistance profiles of Ab isolated from patients in Thong Nhat Dong Nai General Hospital and assess the relationship between genotypes and antibiotic resistance; Methods: Ninety-seven Ab strains isolated from 340 lower respiratory tract specimens among pneumonia patients were used to screen the most common local carbapenemase genes. Antimicrobial susceptibility testing results and demographic data were collected and minimum inhibitory concentrations (MIC) of colistin were also determined; Results: Over 80% and 90% of Ab strains were determined as carbapenem-resistant and multidrug-resistant (MDR), respectively. Most of the strains carried carbapenemase genes, including blaOXA-51, blaOXA-23-like, blaOXA-58-like, and blaNDM-1, with proportions of 97 (100%), 76 (78.4%), 10 (10.3%), 6 (6.2%), respectively. Amongst these genes, blaOXA-23-like was the only gene which significantly influenced the resistance (p < 0.0001); and Conclusions: The severity of Ab antibiotic resistance is urgent and specifically related to carbapenemase encoding genes. Therefore, screening of MDR Ab and carbapenemase for better treatment options is necessary.

scholarly journals Biofilm Formation and Detection of Fluoroquinolone- and Carbapenem-Resistant Genes in Multidrug-Resistant Acinetobacter baumannii

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
María-Guadalupe Avila-Novoa ◽  
Oscar-Alberto Solís-Velázquez ◽  
Daniel-Eduardo Rangel-López ◽  
Jean-Pierre González-Gómez ◽  
Pedro-Javier Guerrero-Medina ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Low Grade ◽  
Carbapenem Resistant ◽  
Hospital Environments ◽  
Potential Association ◽  
Clinical Environments

Acinetobacter baumannii is an important opportunistic pathogen that shows resistance to cephalosporins, penicillins, carbapenems, fluoroquinolones, and aminoglycosides, the multiresistance being associated with its ability to form biofilms in clinical environments. The aim of this study was to determine biofilm formation and its potential association with genes involved in antibiotic resistance mechanisms of A. baumannii isolates of different clinical specimens. We demonstrated 100% of the A. baumannii isolates examined to be multidrug resistant (MDR), presenting a 73.3% susceptibility to cefepime and a 53.3% susceptibility to ciprofloxacin. All A. baumannii isolates were positive for blaOXA-51, 33.3% being positive for blaOXA-23 and ISAba1, and 73.3% being positive for gyrA. We found 86.6% of A. baumannii strains to be low-grade biofilm formers and 13.3% to be biofilm negative; culturing on Congo red agar (CRA) plates revealed that 73.3% of the A. baumannii isolates to be biofilm producers, while 26.6% were not. These properties, combined with the role of A. baumannii as a nosocomial pathogen, increase the probability of A. baumannii causing nosocomial infections and outbreaks as a complication during therapeutic treatments and emphasize the need to control A. baumannii biofilms in hospital environments.

Sign in / Sign up

Export Citation Format

Share Document