Prevalence and molecular mechanisms of colistin resistance in Acinetobacter baumannii clinical isolates in Tehran, Iran

2021 ◽  
Author(s):  
Amin Khoshbayan ◽  
Aref Shariati ◽  
Samane Shahmoradi ◽  
Zohre Baseri ◽  
Haniyeh Mozafari ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Clinical Samples ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Two Component System ◽  
Reverse Transcription Pcr ◽  
Polymerase Chain

AbstractColistin is one of the last remaining active antibiotics against multidrug resistant Gram-negative bacteria. However, several recent studies reported colistin-resistant (ColR) Acinetobacter baumannii from different countries. In the current study, we investigated molecular mechanisms involved in colistin resistance in A. baumannii isolates from different clinical samples.A total of 110 clinical A. baumannii isolates were collected from two hospitals in Tehran. Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to the Clinical and Laboratory Standards Institute. For the ColR isolates, mutation was detected in pmrA, pmrB, lpxA, lpxC, and lpxD genes using the polymerase chain reaction (PCR) and sequencing. Moreover, the relative expression of the pmrC gene was calculated using quantitative reverse transcription PCR. Three colistin resistant isolates were identified with MIC between 8 and 16 μg/mL and were resistant to all the tested antimicrobial agents. All the three isolates had a mutation in the pmrB, pmrA, lpxA, lpxD, and lpxC genes. Moreover, the overexpression of pmrC gene was observed in all isolates. Our results showed that the upregulation of the PmrAB two component system was the primary mechanism linked to colistin resistance among the studied colistin resistant A. baumannii isolates.

scholarly journals Real-Time Sequencing To Decipher the Molecular Mechanism of Resistance of a Clinical Pan-Drug-Resistant Acinetobacter baumannii Isolate from Marseille, France

2012 ◽  
Vol 57 (1) ◽  
pp. 592-596 ◽  
Author(s):  
Jean-Marc Rolain ◽  
Seydina M. Diene ◽  
Marie Kempf ◽  
Gregory Gimenez ◽  
Catherine Robert ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Two Component System ◽  
Genome Sequences ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Baumannii Isolate

ABSTRACTWe compare the whole-genome sequences of two multidrug-resistant clinicalAcinetobacter baumanniiisolates recovered in the same patient before (ABIsac_ColiS susceptible to colistin and rifampin only) and after (ABIsac_ColiR resistant to colistin and rifampin) treatment with colistin and rifampin. We decipher all the molecular mechanisms of antibiotic resistance, and we found mutations in therpoBgene and in the PmrAB two-component system explaining resistance to rifampin and colistin in ABIsac_ColiR, respectively.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

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.

scholarly journals Evaluation of Moringa Peregrina (Forsk) Fiori, Leaf and Seed Extract Against Multidrug Resistant Strains of Bacteria and Fungus of Clinical Origin

2021 ◽  
Vol 3 (1) ◽  
pp. 20-26
Author(s):  
Suliman Mansour Albalawi ◽  
Abdulrahman K. Al-Asmari ◽  
Syed Rafatullah ◽  
Maysa Mahfoud
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Growth Inhibition ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Colorimetric Assay ◽  
Multidrug Resistant ◽  
Klebsiella Pneumonia ◽  
Isolation And Purification ◽  
Moringa Peregrina

  The emergence of antibiotic resistant microorganism strains has become a critical concern in the treatment of infectious diseases and makes the search of an alternative therapy a must. The study was designed to evaluate the in vitro antimicrobial activities of the Moringa peregrina (MP) leave (MPL) and seed (MPS) extracts. Antimicrobial assays were performed using a microplate growth inhibition assay against 11 multidrug-resistant (MDR) strains. Following qualitative analysis, dose-response assays were performed using the MTT colorimetric assay. The results showed a strong correlation between the MPL and MPS extract concentration and growth inhibition (P<0.001). MP extract revealed a remarkable antimicrobial effect and inhibited the growth and survival of MDR pathogens which include Escherichia coli; Pseudomonas aeruginosa; Klebsiella pneumonia; Acinetobacter baumannii; Staphylococcus aureus between (88.6-94.7 %) and between (62.3- 88.7%) against Candida Kefyer; Candida parapsilosis; Candida albicans; Candida glabrata; Aspergillus flavus and Fusarium oxysporum. MIC50 ranging from ≤6.25 to 25 mg/mL. Acinetobacter baumannii and Pseudomonas aeruginosa were the most susceptible to MP extracts (MIC50 < 6.25 mg/mL). These results support the use of MP in Arab traditional medicine as natural antimicrobial agents. Additionally, the use of such naturally occurring adjuvant derived from medicinal plants can be used as an adjuvant with synthetic antibiotics to combat bacterial resistance and to enhance the antibacterial potential. Further studies are recommended on isolation and purification of novel antimicrobial molecules to treat the infections caused by microbes.  

scholarly journals Heterogeneous and Flexible Transmission ofmcr-1in Hospital-AssociatedEscherichia coli

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Yingbo Shen ◽  
Zuowei Wu ◽  
Yang Wang ◽  
Rong Zhang ◽  
Hong-Wei Zhou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Genes Encoding

ABSTRACTThe recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route ofmcr-1amongEnterobacteriaceaespecies in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis ofEscherichia coliisolates collected in a hospital in Hangzhou, China. We found thatmcr-1-carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread ofmcr-1. Themcr-1gene was found on either chromosomes or plasmids, but in most of theE. coliisolates,mcr-1was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission ofmcr-1and the coexistence ofmcr-1with other genes encoding β-lactamases and fluoroquinolone resistance in theE. coliisolates. These findings indicate thatmcr-1is heterogeneously disseminated in both commensal and pathogenic strains ofE. coli, suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology ofmcr-1among hospital-associatedE. colistrains.IMPORTANCEColistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergentmcr-1colistin resistance gene threatens the clinical utility of colistin and has gained global attention. Howmcr-1spreads in hospital settings remains unknown and was investigated by whole-genome sequencing ofmcr-1-carryingEscherichia coliin this study. The findings revealed extraordinary flexibility ofmcr-1in its spread among genetically diverseE. colihosts and plasmids, nosocomial transmission ofmcr-1-carryingE. coli, and the continuous emergence of novel Inc types of plasmids carryingmcr-1and newmcr-1variants. Additionally,mcr-1was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology ofmcr-1and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.

scholarly journals Functional Characterization of AbaQ, a Novel Efflux Pump Mediating Quinolone Resistance inAcinetobacter baumannii

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
María Pérez-Varela ◽  
Jordi Corral ◽  
Jesús Aranda ◽  
Jordi Barbé
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Functional Characterization ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Mfs Transporter

ABSTRACTAcinetobacter baumanniihas emerged as an important multidrug-resistant nosocomial pathogen. In previous work, we identified a putative MFS transporter, AU097_RS17040, involved in the pathogenicity ofA. baumannii(M. Pérez-Varela, J. Corral, J. A. Vallejo, S. Rumbo-Feal, G. Bou, J. Aranda, and J. Barbé, Infect Immun 85:e00327-17, 2017,https://doi.org/10.1128/IAI.00327-17). In this study, we analyzed the susceptibility to diverse antimicrobial agents ofA. baumanniicells defective in this transporter, referred to as AbaQ. Our results showed that AbaQ is mainly involved in the extrusion of quinolone-type drugs inA. baumannii.

scholarly journals Tigecycline susceptibility of multidrug-resistant Acinetobacter baumannii from intensive care units in the western Balkans

2020 ◽  
Vol 67 (3) ◽  
pp. 176-181
Author(s):  
Ina Gajic ◽  
Lazar Ranin ◽  
Dusan Kekic ◽  
Natasa Opavski ◽  
Aleksandra Smitran ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Inappropriate Therapy ◽  
Antibiotic Susceptibility Testing ◽  
Broth Microdilution ◽  
Western Balkans ◽  
Colistin Resistance ◽  
European Committee ◽  
Carbapenem Resistant

AbstractTigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 μg/mL by BMD and 0.5/4 μg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.

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