scholarly journals Cloning, expression, purification and functional analysis of a specific multi-epitope protein from multi drug resistance Acinetobacter baumannii

2021 ◽  
Author(s):  
Zahra Davoudi ◽  
Amirhossein Taromchi ◽  
Bahram Kazemi ◽  
Mojgan Bandehpour ◽  
Nariman Mosaffa
Keyword(s):  
Drug Resistance ◽  
Recombinant Protein ◽  
Acinetobacter Baumannii ◽  
Cloning And Expression ◽  
Multi Drug Resistance ◽  
Expression And Purification ◽  
Bam Complex ◽  
Promising Strategy ◽  
Life Threatening ◽  
Informatics Tools

Background and Objectives: Immunization is a promising strategy to combat against the life-threatening infections by Multi Drug Resistance Acinetobacter baumannii. In this study, we directed to design and evaluate the efficacy of a recombi- nant multi-epitope protein against this pathogen. Materials and Methods: Epitopes prediction was performed for candidate proteins OmpA and BAM complex (BamA, BamB, BamC, BamD, BamE) from A. baumannii, using immune-informatics tools with high affinity for the human HLA alleles. After expression and purification of the recombinant protein, its functional activity was confirmed by interaction with positive sera. Results: Cloning and expression of the desired multi-epitopes protein were verified. Circular Dichroism study showed the secondary structure and proper refolding of the recombinant protein was achieved and matched with computational predic- tion. There was a significant interaction between designed protein with antibodies presented in ICU patients' and staff's sera. Conclusion: The interaction of the recombinant protein with patients' sera antibodies suggests that it may be a promising determinant protein for immunization against of MDR A. baumannii.

scholarly journals Impact of an Intervention to Control Imipenem-Resistant Acinetobacter baumannii and Its Resistance Mechanisms: An 8-Year Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Lida Chen ◽  
Pinghai Tan ◽  
Jianming Zeng ◽  
Xuegao Yu ◽  
Yimei Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Minimal Inhibitory Concentrations ◽  
Resistance Rates ◽  
The Impact

BackgroundThis study aimed to examine the impact of an intervention carried out in 2011 to combat multi-drug resistance and outbreaks of imipenem-resistant Acinetobacter baumannii (IRAB), and to explore its resistance mechanism.MethodsA total of 2572 isolates of A. baumannii, including 1673 IRAB isolates, were collected between 2007 and 2014. An intervention was implemented to control A. baumannii resistance and outbreaks. Antimicrobial susceptibility was tested by calculating minimal inhibitory concentrations (MICs), and outbreaks were typed using pulsed-field gel electrophoresis (PFGE). Resistance mechanisms were explored by polymerase chain reaction (PCR) and whole genome sequencing (WGS).ResultsFollowing the intervention in 2011, the resistance rates of A. baumannii to almost all tested antibiotics decreased, from 85.3 to 72.6% for imipenem, 100 to 80.8% for ceftriaxone, and 45.0 to 6.9% for tigecycline. The intervention resulted in a decrease in the number (seven to five), duration (8–3 months), and departments (five to three) affected by outbreaks; no outbreaks occurred in 2011. After the intervention, only blaAMPC (76.47 to 100%) and blaTEM–1 (75.74 to 96.92%) increased (P < 0.0001); whereas blaGES–1 (32.35 to 3.07%), blaPER–1 (21.32 to 1.54%), blaOXA–58 (60.29 to 1.54%), carO (37.50 to 7.69%), and adeB (9.56 to 3.08%) decreased (P < 0.0001). Interestingly, the frequency of class B β-lactamase genes decreased from 91.18% (blaSPM–1) and 61.03% (blaIMP–1) to 0%, while that of class D blaOXA–23 increased to 96.92% (P < 0.0001). WGS showed that the major PFGE types causing outbreaks each year (type 01, 11, 18, 23, 26, and 31) carried the same resistance genes (blaKPC–1, blaADC–25, blaOXA–66, and adeABC), AdeR-S mutations (G186V and A136V), and a partially blocked porin channel CarO. Meanwhile, plasmids harboring blaOXA–23 were found after the intervention.ConclusionThe intervention was highly effective in reducing multi-drug resistance of A. baumannii and IRAB outbreaks in the long term. The resistance mechanisms of IRAB may involve genes encoding β-lactamases, efflux pump overexpression, outer membrane porin blockade, and plasmids; in particular, clonal spread of blaOXA–23 was the major cause of outbreaks. Similar interventions may also help reduce bacterial resistance rates and outbreaks in other hospitals.

scholarly journals Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jing He ◽  
Xiao-Yan Shi ◽  
Zhi-min Li ◽  
Xiao-hua Pan ◽  
Ze-Lian Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Epithelial Ovarian Carcinoma ◽  
Cytotoxic Agents ◽  
Multi Drug Resistance ◽  
Paclitaxel Resistance ◽  
Promising Strategy ◽  
Lethal Doses

Abstract Background Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. . Results We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells. Conclusions These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.

scholarly journals Efficacy of Isolated Bacteriophage Against Biofilm Embedded Colistin-Resistant Acinetobacter baumannii

2020 ◽  
Author(s):  
Saeedeh Ebrahimi ◽  
Behnam Sisakhtpour ◽  
Arezoo Mirzaei ◽  
Vajihe Karbasizadeh ◽  
Sharareh Moghim
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Phage Therapy ◽  
Pathogen Resistance ◽  
Multi Drug Resistance ◽  
Lytic Phage ◽  
Resistant Strains ◽  
High Degree

Abstract Objective: Acinetobacter baumannii is responsible for most nosocomial infections in hospitals. It has the ability to form biofilms and has a high degree of antibiotic resistance. Colistin is one of the last therapeutic options for the treatment of Multi Drug Resistance infections. Recently, strains of this pathogen resistance to the colistin were reported increasingly. Therefore, alternative antibacterial methods such as phage therapy are being researched. Results: From 15 MDR A. baumannii clinical isolates, 26.6% were resistant to colistin, 80% were able to produce strong biofilm, and 20% produce weak biofilm. The isolated lytic phage (IsfAB78) was able to reduce the biofilm by up to 87%. Since most of the MDR colistin-resistant strains produce biofilm, and MDR A. baumannii infections are difficult to treat, development of phage therapy could be an alternative in the future. Phage IsfAB78 is a good candidate for this purpose.

scholarly journals Micafungin Is an Efficient Treatment of Multi Drug-Resistant Candida glabrata Urosepsis: A Case Report

2021 ◽  
Vol 7 (10) ◽  
pp. 800
Author(s):  
Zuzana Javorova Rihova ◽  
Lubica Slobodova ◽  
Anna Hrabovska
Keyword(s):  
Drug Resistance ◽  
Urinary Tract ◽  
Candida Glabrata ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Candida Spp ◽  
Efficient Treatment ◽  
Pharmacokinetic Properties ◽  
Life Threatening ◽  
Low Levels

Candiduria is a common nosocomial infection in hospitalized patients, which may progress into life-threatening candidemia. Successful treatment of urosepsis requires early and effective antifungal therapy, while the available agents within three pharmacological classes each have characteristic pharmacokinetics and side effect profiles. Moreover, treatment of Candida spp. infections is becoming challenging due to increasing multi drug-resistance. Here, we present a case of candidemia resulting from a multi drug-resistant C. glabrata infection of the urinary tract. Due to resistance to fluconazole and a contraindication for amphotericin B, micafungin was used in the treatment, regardless of its unfavorable pharmacokinetic properties. Our study showed that despite the expected low levels in the urinary tract, micafungin was successful in the eradication of C. glabrata allowing full recovery of the patient. Thus, micafungin should be considered in the management of urosepsis caused by sensitive Candida spp.

scholarly journals Phenotypic and Molecular detection of Acinetobacter baumannii isolated from patients in Duhok city-Iraq

2019 ◽  
Vol 7 (4) ◽  
pp. 132-137
Author(s):  
Zainab H. Abdullah ◽  
Narmin S. Merza
Keyword(s):  
Drug Resistance ◽  
16S Rrna ◽  
Acinetobacter Baumannii ◽  
Molecular Techniques ◽  
The Other ◽  
Diffusion Method ◽  
Resistance Testing ◽  
Multi Drug Resistance ◽  
Clinical Samples ◽  
Identification System

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen and one of the most importnat Multidrug resistant microorganisms responsible for a vast array of nosocomial infections. 41 (6.8 %) isolates of A.  baumannii were obtained from a total of 603 clinical samples of burn and sputum during the period from March 2018 to February 2019. Twenty two isolates (3.6%) of A. baummanni were recovered from burn infections and nineteen isolates (3.2%) from sputum specimens. Identification and characterization of these isolates was accomplished by the aid of selective media (CHROM agar Acinetobacter) and was finally confirmed by VITEK 2 identification system test. Molecular identification utilizing genus and species-specific primers to detect the 16S rRNA and blaOXA-51 was also applied.  The Antibiotic resistance testing was done by the Kirby-Bauer disc diffusion method, 24 .4% of the isolates were Multi-Drug Resistance (MDR), while 65.9% were extensive drug resistance (XDR). All isolates  were absolutely resistant (100 %) to most of the antibiotics in use: cefixime, cefotaxime, ceftriaxone, ceftazidime, piperacillin-tazobactam, amoxicillin-tazobactam, while the resistant profile for the other antibiotics can be represented as follows 98 %, 95 %, 90 %, and 83 % For both ciprofloxacin and norfloxacin, gentamycin and meropenem, amikacin, and azithromycin and imipenem, respectively. On the other hand, levofloxacin has a moderate effect on the isolates shown by 51% resistant isolates followed by doxycycline for which 39% of the isolates were resistant. Colistin was the only antimicrobial agent that has an intense effect as the majority of the isolates were sensitive. All the selected isolates of A. baumannii were successfuly produced band corresponded to the intended genes. Accurate and early detection of such bacteria is essential for stimulates effective treatment specifically in intensive care units. Molecular techniques have been successfully applied with high specificity using 16S rRNA and blaOXA-51-like gene as a simple and reliable method to differentiate  A. baumannii strains.

scholarly journals Multi-drug resistance profiles and the genetic features of Acinetobacter baumannii isolates from Bolivia

2013 ◽  
Vol 7 (04) ◽  
pp. 323-328 ◽  
Author(s):  
Bruno Silvester Lopes ◽  
Lucia Gallego ◽  
Sebastian Giles Becket Amyes
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Efflux Pump ◽  
Fluoroquinolone Resistance ◽  
Multi Drug Resistance ◽  
Resistance Mutations ◽  
Aminoglycoside Resistance ◽  
Over Expression ◽  
Hospitalised Patients

Introduction: Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009. Methodology: Multiplex PCR was used to identify the main resistance genes in 15 multi-resistant A. baumannii isolates. RT-PCR was used to measure gene expression. The genetic environment of these genes was also analysed by PCR amplification and sequencing. Minimum inhibitory concentrations were determined for key antibiotics and some were determined in the presence of an efflux pump inhibitor, 1-(1-napthylmethyl) piperazine. Results: Fourteen strains were found to be multi-resistant. Each strain was found to have the blaOXA-58 gene with the ISAba3-like element upstream, responsible for over-expression of the latter and subsequent carbapenem resistance. Similarly, ISAba1, upstream of the blaADC gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance. In addition, the adeA, adeB efflux genes were over-expressed. All 15 isolates were positive for at least two aminoglycoside resistance genes. Conclusion: This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of theblaOXA-58, blaADC and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA topoisomerases are responsible for the multi-resistance of the bacteria and the subsequent difficulty in treating infections caused by them.

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