scholarly journals Microbicides Alter the Expression and Function of RND-Type Efflux Pump AdeABC in Biofilm-Associated Cells of Acinetobacter baumannii Clinical Isolates

2015 ◽  
Vol 60 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Suvarna Krishnamoorthy ◽  
Bhavikkumar P. Shah ◽  
Hiu Ham Lee ◽  
Luis R. Martinez
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Content Type ◽  
Abiotic Surfaces ◽  
Hospital Environments ◽  
And Function

ABSTRACTAcinetobacter baumanniiis a Gram-negative bacterium that causes nosocomial infections worldwide. This microbe's propensity to form biofilms allows it to persist and to survive on clinical abiotic surfaces for long periods. In fact,A. baumanniibiofilm formation and its multidrug-resistant nature severely compromise our capacity to care for patients in hospital environments. In contrast, microbicides such as cetrimide (CT) and chlorhexidine (CHX) play important roles in the prevention and treatment of infections. We assessed the efficacy of CT and CHX, either alone or in combination, in eradicatingA. baumanniibiofilms formed by clinical isolates, by using stainless steel washers to mimic hard abiotic surfaces found in hospital settings. We demonstrated that increasing amounts of each microbicide, alone or in combination, were able to damage and to reduce the viability ofA. baumanniibiofilms efficaciously. Interestingly, theadeBgene of the resistance-nodulation-cell division (RND) family is predominantly associated with acquired resistance to antimicrobials inA. baumannii. We showed that CT and CHX adversely modified the expression and function of the RND-type efflux pump AdeABC in biofilm-associatedA. baumanniicells. Furthermore, we established that these microbicides decreased the negative charges onA. baumanniicell membranes, causing dysregulation of the efflux pump and leading to cell death. Our findings suggest that CT and CHX, alone or in combination, can be used efficaciously for eradication ofA. baumanniifrom hospital surfaces, in order to reduce infections caused by this nosocomial agent.

scholarly journals Molecular Analysis of the Acinetobacter baumannii Biofilm-Associated Protein

2013 ◽  
Vol 79 (21) ◽  
pp. 6535-6543 ◽  
Author(s):  
H. M. Sharon Goh ◽  
Scott A. Beatson ◽  
Makrina Totsika ◽  
Danilo G. Moriel ◽  
Minh-Duy Phan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Biofilm Growth ◽  
Content Type ◽  
Amino Acid Region ◽  
Carbapenem Resistant ◽  
C Terminus ◽  
And Function

ABSTRACTAcinetobacter baumanniiis a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability ofA. baumanniito survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of theA. baumanniibiofilm-associated protein (Bap) in 24 carbapenem-resistantA. baumanniiST92 strains isolated from a single institution over a 10-year period. Thebapgene was highly prevalent, with 22/24 strains being positive forbapby PCR. Partial sequencing ofbapwas performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that BapMS1968clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, thebapMS1968gene was cloned, and its expression in a recombinantEscherichia colistrain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority ofA. baumanniistrains expressed an ∼200-kDa Bap protein. Further analysis of three Bap-positiveA. baumanniistrains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth byA. baumanniiclinical isolates.

scholarly journals Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate

2015 ◽  
Vol 60 (3) ◽  
pp. 1370-1376 ◽  
Author(s):  
Ghulam Nasser Dhabaan ◽  
Sazaly AbuBakar ◽  
Gustavo Maia Cerqueira ◽  
Mohammed Al-Haroni ◽  
Sui Ping Pang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Clinical Success ◽  
Multidrug Resistant ◽  
Type Iv Pili ◽  
Control Measures ◽  
Content Type ◽  
Type Iv ◽  
Abiotic Surfaces ◽  
Colonization Factors

Acinetobacter baumanniihas emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential forA. baumanniiadherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Impr) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imps) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imprbut not in the Impsisolate. Notably, this finding is corroborated by an increase in the motility of the Imprstrain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage toA. baumanniiand may contribute to clinical success.

scholarly journals RND-Type Efflux Pumps in Multidrug-Resistant Clinical Isolates of Acinetobacter baumannii: Major Role for AdeABC Overexpression and AdeRS Mutations

2013 ◽  
Vol 57 (7) ◽  
pp. 2989-2995 ◽  
Author(s):  
Eun-Jeong Yoon ◽  
Patrice Courvalin ◽  
Catherine Grillot-Courvalin
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Regulatory System ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Two Component System ◽  
Content Type ◽  
High Incidence ◽  
Two Component

ABSTRACTIncreased expression of chromosomal genes for resistance-nodulation-cell division (RND)-type efflux systems plays a major role in the multidrug resistance (MDR) ofAcinetobacter baumannii. However, the relative contributions of the three most prevalent pumps, AdeABC, AdeFGH, and AdeIJK, have not been evaluated in clinical settings. We have screened 14 MDR clinical isolates shown to be distinct on the basis of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) for the presence and overexpression of the three Ade efflux systems and analyzed the sequences of the regulators AdeRS, a two-component system, for AdeABC and AdeL, a LysR-type regulator, for AdeFGH. GeneadeBwas detected in 13 of 14 isolates, andadeGand the intrinsicadeJgene were detected in all strains. Significant overexpression ofadeBwas observed in 10 strains, whereas only 7 had moderately increased levels of expression of AdeFGH, and none overexpressed AdeIJK. Thirteen strains had reduced susceptibility to tigecycline, but there was no correlation between tigecycline MICs and the levels of AdeABC expression, suggesting the presence of other mechanisms for tigecycline resistance. No mutations were found in the highly conserved LysR regulator of the nine strains expressing AdeFGH. In contrast, functional mutations were found in conserved domains of AdeRS in all the strains that overexpressed AdeABC with two mutational hot spots, one in AdeS near histidine 149 suggesting convergent evolution and the other in the DNA binding domain of AdeR compatible with horizontal gene transfer. This report outlines the high incidence of AdeABC efflux pump overexpression in MDRA. baumanniias a result of a variety of single mutations in the corresponding two-component regulatory system.

scholarly journals Biofilm Formation Caused by Clinical Acinetobacter baumannii Isolates Is Associated with Overexpression of the AdeFGH Efflux Pump

2015 ◽  
Vol 59 (8) ◽  
pp. 4817-4825 ◽  
Author(s):  
Xinlong He ◽  
Feng Lu ◽  
Fenglai Yuan ◽  
Donglin Jiang ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Gene Transcription ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Outer Membrane Proteins ◽  
Content Type ◽  
Potential Association ◽  
Genes Encoding ◽  
Clinical Environments

ABSTRACTChronic wound infections are associated with biofilm formation, which in turn has been correlated with drug resistance. However, the mechanism by which bacteria form biofilms in clinical environments is not clearly understood. This study was designed to investigate the biofilm formation potency ofAcinetobacter baumanniiand the potential association of biofilm formation with genes encoding efflux pumps, quorum-sensing regulators, and outer membrane proteins. A total of 48 clinically isolatedA. baumanniistrains, identified by enterobacterial repetitive intergenic consensus (ERIC)-PCR as types A-II, A-III, and A-IV, were analyzed. Three representative strains, which were designatedA. baumanniiABR2, ABR11, and ABS17, were used to evaluate antimicrobial susceptibility, biofilm inducibility, and gene transcription (abaI,adeB,adeG,adeJ,carO, andompA). A significant increase in the MICs of different classes of antibiotics was observed in the biofilm cells. The formation of a biofilm was significantly induced in all the representative strains exposed to levofloxacin. The levels of gene transcription varied between bacterial genotypes, antibiotics, and antibiotic concentrations. The upregulation ofadeGcorrelated with biofilm induction. The consistent upregulation ofadeGandabaIwas detected in A-III-typeA. baumanniiin response to levofloxacin and meropenem (1/8 to 1/2× the MIC), conditions which resulted in the greatest extent of biofilm induction. This study demonstrates a potential role of the AdeFGH efflux pump in the synthesis and transport of autoinducer molecules during biofilm formation, suggesting a link between low-dose antimicrobial therapy and a high risk of biofilm infections caused byA. baumannii. This study provides useful information for the development of antibiofilm strategies.

scholarly journals In Vitro Activity of Sulbactam-Durlobactam against Acinetobacter baumannii-calcoaceticus Complex Isolates Collected Globally in 2016 and 2017

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sarah M. McLeod ◽  
Samir H. Moussa ◽  
Meredith A. Hackel ◽  
Alita A. Miller
Keyword(s):  
Acinetobacter Baumannii ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Single Amino Acid ◽  
Content Type ◽  
Level Of Activity ◽  
Severe Infections ◽  
Sources Of Infection

ABSTRACT Acinetobacter baumannii-calcoaceticus complex (ABC) organisms cause severe infections that are difficult to treat due to preexisting antibiotic resistance. Sulbactam-durlobactam (formerly sulbactam-ETX2514) (SUL-DUR) is a β-lactam–β-lactamase inhibitor combination antibiotic designed to treat serious infections caused by ABC organisms, including multidrug-resistant (MDR) strains. The in vitro antibacterial activities of SUL-DUR and comparator agents were determined by broth microdilution against 1,722 clinical isolates of ABC organisms collected in 2016 and 2017 from 31 countries across Asia/South Pacific, Europe, Latin America, the Middle East, and North America. Over 50% of these isolates were resistant to carbapenems. Against this collection of global isolates, SUL-DUR had a MIC50/MIC90 of 1/2 μg/ml compared to a MIC50/MIC90 of 8/64 μg/ml for sulbactam alone. This level of activity was found to be consistent across organisms, regions, sources of infection, and subsets of resistance phenotypes, including MDR and extensively drug-resistant isolates. The SUL-DUR activity was superior to those of the tested comparators, with only colistin having similar potency. Whole-genome sequencing of the 39 isolates (2.3%) with a SUL-DUR MIC of >4 μg/ml revealed that these strains encoded either the metallo-β-lactamase NDM-1, which durlobactam does not inhibit, or single amino acid substitutions near the active site of penicillin binding protein 3 (PBP3), the primary target of sulbactam. In summary, SUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC organisms, including MDR isolates.

Efflux pump inhibitory activity of biologically synthesized silver nanoparticles against multidrug-resistant Acinetobacter baumannii clinical isolates

2020 ◽  
Vol 60 (6) ◽  
pp. 494-507 ◽  
Author(s):  
Reyhaneh Behdad ◽  
Minoo Pargol ◽  
Amir Mirzaie ◽  
Shohreh Zare Karizi ◽  
Hassan Noorbazargan ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Acinetobacter Baumannii ◽  
Inhibitory Activity ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Clinical Isolates

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 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.

scholarly journals Contribution of Resistance-Nodulation-Division Efflux Pump OperonsmeU1-V-W-U2-Xto Multidrug Resistance of Stenotrophomonas maltophilia

2011 ◽  
Vol 55 (12) ◽  
pp. 5826-5833 ◽  
Author(s):  
Chao-Hsien Chen ◽  
Chiang-Ching Huang ◽  
Tsao-Chuen Chung ◽  
Rouh-Mei Hu ◽  
Yi-Wei Huang ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Type Systems ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Content Type ◽  
Membrane Fusion Protein ◽  
Resistance Nodulation Division

ABSTRACTKJ09C, a multidrug-resistant mutant ofStenotrophomonas maltophiliaKJ, was generated byin vitroselection with chloramphenicol. The multidrug-resistant phenotype of KJ09C was attributed to overexpression of a resistance nodulation division (RND)-type efflux system encoded by an operon consisting of five genes:smeU1,smeV,smeW,smeU2, andsmeX. Proteins encoded bysmeV,smeW, andsmeXwere similar to the membrane fusion protein, RND transporter, and outer membrane protein, respectively, of known RND-type systems. The proteins encoded bysmeU1andsmeU2were found to belong to the family of short-chain dehydrogenases/reductases. Mutant KJ09C exhibited increased resistance to chloramphenicol, quinolones, and tetracyclines and susceptibility to aminoglycosides; susceptibility to β-lactams and erythromycin was not affected. The expression of thesmeU1-V-W-U2-Xoperon was regulated by the divergently transcribed LysR-type regulator genesmeRv. Overexpression of the SmeVWX pump contributed to the acquired resistance to chloramphenicol, quinolones, and tetracyclines. Inactivation ofsmeVandsmeWcompletely abolished the activity of the SmeVWX pump, whereas inactivation ofsmeXalone decreased the activity of the SmeVWX pump. The enhanced aminoglycoside susceptibility observed in KJ09C resulted from SmeX overexpression.

scholarly journals Draft Genome Sequences of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii

2017 ◽  
Vol 5 (5) ◽  
Author(s):  
Keesha E. Erickson ◽  
Nancy E. Madinger ◽  
Anushree Chatterjee
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Genome Sequences ◽  
Content Type ◽  
University Of Colorado ◽  
The University

ABSTRACT We report here the draft genome sequences of two clinically isolated Acinetobacter baumannii strains. These samples were obtained from patients at the University of Colorado Hospital in 2007 and 2013 and encode an estimated 20 and 13 resistance genes, respectively.

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