scholarly journals The Role of the CopA Copper Efflux System in Acinetobacter baumannii Virulence

2019 ◽  
Vol 20 (3) ◽  
pp. 575 ◽  
Author(s):  
Saleh Alquethamy ◽  
Marjan Khorvash ◽  
Victoria Pederick ◽  
Jonathan Whittall ◽  
James Paton ◽  
...  

Acinetobacter baumannii has emerged as one of the leading causative agents of nosocomial infections. Due to its high level of intrinsic and adapted antibiotic resistance, treatment failure rates are high, which allows this opportunistic pathogen to thrive during infection in immune-compromised patients. A. baumannii can cause infections within a broad range of host niches, with pneumonia and bacteraemia being associated with the greatest levels of morbidity and mortality. Although its resistance to antibiotics is widely studied, our understanding of the mechanisms required for dealing with environmental stresses related to virulence and hospital persistence, such as copper toxicity, is limited. Here, we performed an in silico analysis of the A. baumannii copper resistome, examining its regulation under copper stress. Using comparative analyses of bacterial P-type ATPases, we propose that A. baumannii encodes a member of a novel subgroup of P1B-1 ATPases. Analyses of three putative inner membrane copper efflux systems identified the P1B-1 ATPase CopA as the primary mediator of cytoplasmic copper resistance in A. baumannii. Using a murine model of A. baumannii pneumonia, we reveal that CopA contributes to the virulence of A. baumannii. Collectively, this study advances our understanding of how A. baumannii deals with environmental copper toxicity, and it provides novel insights into how A. baumannii combats adversities encountered as part of the host immune defence.

2010 ◽  
Vol 54 (8) ◽  
pp. 3484-3488 ◽  
Author(s):  
José-Manuel Rodríguez-Martínez ◽  
Patrice Nordmann ◽  
Esthel Ronco ◽  
Laurent Poirel

ABSTRACT An AmpC-type β-lactamase conferring high-level resistance to expanded-spectrum cephalosporins and monobactams was characterized from an Acinetobacter baumannii clinical isolate. This class C β-lactamase (named ADC-33) possessed a Pro210Arg substitution together with a duplication of an Ala residue at position 215 (inside the Ω-loop) compared to a reference AmpC cephalosporinase from A. baumannii. ADC-33 hydrolyzed ceftazidime, cefepime, and aztreonam at high levels, which allows the classification of this enzyme as an extended-spectrum AmpC (ESAC). Site-directed mutagenesis confirmed the role of both substitutions in its ESAC property.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kelly Conde-Pérez ◽  
Juan C. Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Lucía Ageitos ◽  
Soraya Rumbo-Feal ◽  
...  

Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes entA, basG, basC, basD, and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA, coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔbasJ/ΔfbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA, basG, basC, basD, basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.


2008 ◽  
Vol 133 (5) ◽  
pp. 670-677 ◽  
Author(s):  
Jie Li ◽  
Scott M. Leisner ◽  
Jonathan Frantz

Copper (Cu) is an essential micronutrient for plants and is the a.i. in pesticides for some pathogens and algae. Elevated doses of Cu can cause toxicity in plants. While silicon (Si) is reported to alleviate the toxicity of some heavy metals, its role in reducing the symptoms induced by excess Cu is unclear. Therefore, the role of Si in plant response to Cu stress was investigated in arabidopsis [Arabidopsis thaliana (L.) Heyn.]. Based on plant symptoms (a reduction of leaf chlorosis as well as increased shoot and root biomass) and a reduction of phenylalanine ammonia lyase [PAL (EC 4.3.1.5), a stress-induced enzyme] activity in the shoot, Si was found to alleviate copper stress. Real-time reverse transcriptase-polymerase chain reaction analyses indicated that the RNA levels of two arabidopsis copper transporter genes, copper transporter 1 (COPT1) and heavy metal ATPase subunit 5 (HMA5) were induced by high levels of Cu, but were significantly decreased when Si levels were also elevated. Taken together, our findings indicate that Si addition can improve the resistance of arabidopsis to Cu stress, and this improvement operates on multiple levels, ranging from physiological changes to alterations of gene expression.


2020 ◽  
Vol 20 (4) ◽  
pp. 501-505
Author(s):  
Debarati Paul ◽  
Swarupa Mallick ◽  
Swati Das ◽  
Suman Saha ◽  
Ananta K. Ghosh ◽  
...  

Background: Colistin was considered as the most effective antibiotic against Acinetobacter baumannii, a widely-known opportunistic pathogen. In recent years, a number of colistin resistant strains have also been reported. Objective: This work is commenced to investigate the contribution of efflux pumps toward resistance to colistin-like cyclic polypeptide antibiotics, since the efflux pumps serve as the escape routes leading to drug-resistance. Methods: RNA was extracted from A. baumannii isolates cultured from samples procured by tracheal aspiration of infected patients. The expressions of gene(s) that played major roles in the regulation of efflux pump families and involvement of integron systems were studied using real time PCR. Antimicrobial susceptibility tests were conducted to investigate antibiotic resistance of the isolates. Results: It was observed that genes coding for sugE, ydhE, ydgE, mdfA, ynfA and tolC significantly contributed to resistance against colistin antibiotics, however, no significant transcriptional change was observed in the efflux pump, MexAB-OprM. Results suggest that A. baumanii readily pumps out colistin via efflux pumps belonging to MATE and SMR family. Conclusion: Integral role of efflux pumps and integron 1 genetic system was elucidated towards evolution of multi-drug resistant strain(s). Therefore, for accurate therapeutics, an early detection of efflux genes is crucial before prescribing against colistin resistant A. baumanii.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 596
Author(s):  
Diego Lucas Neres Rodrigues ◽  
Francielly Morais-Rodrigues ◽  
Raquel Hurtado ◽  
Roselane Gonçalves dos Santos ◽  
Daniela Camargos Costa ◽  
...  

Acinetobacter baumannii is an important Gram-negative opportunistic pathogen that is responsible for many nosocomial infections. This etiologic agent has acquired, over the years, multiple mechanisms of resistance to a wide range of antimicrobials and the ability to survive in different environments. In this context, our study aims to elucidate the resistome from the A. baumannii strains based on phylogenetic, phylogenomic, and comparative genomics analyses. In silico analysis of the complete genomes of A. baumannii strains was carried out to identify genes involved in the resistance mechanisms and the phylogenetic relationships and grouping of the strains based on the sequence type. The presence of genomic islands containing most of the resistance gene repertoire indicated high genomic plasticity, which probably enabled the acquisition of resistance genes and the formation of a robust resistome. A. baumannii displayed an open pan-genome and revealed a still constant genetic permutation among their strains. Furthermore, the resistance genes suggest a specific profile within the species throughout its evolutionary history. Moreover, the current study performed screening and characterization of the main genes present in the resistome, which can be used in applied research to develop new therapeutic methods to control this important bacterial pathogen.


Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 844
Author(s):  
Sergio Barahona ◽  
Juan Castro-Severyn ◽  
Cristina Dorador ◽  
Claudia Saavedra ◽  
Francisco Remonsellez

The use of microorganisms in mining processes is a technology widely employed around the world. Leaching bacteria are characterized by having resistance mechanisms for several metals found in their acidic environments, some of which have been partially described in the Acidithiobacillus genus (mainly on ferrooxidans species). However, the response to copper has not been studied in the psychrotolerant Acidithiobacillus ferrivorans strains. Therefore, we propose to elucidate the response mechanisms of A. ferrivorans ACH to high copper concentrations (0–800 mM), describing its genetic repertoire and transcriptional regulation. Our results show that A. ferrivorans ACH can grow in up to 400 mM of copper. Moreover, we found the presence of several copper-related makers, belonging to cop and cus systems, as well as rusticyanins and periplasmatic acop protein in the genome. Interestingly, the ACH strain is the only one in which we find three copies of copB and copZ genes. Moreover, transcriptional expression showed an up-regulation response (acop, copZ, cusA, rusA, and rusB) to high copper concentrations. Finally, our results support the important role of these genes in A. ferrivorans copper stress resistance, promoting the use of the ACH strain in industrial leaching under low temperatures, which could decrease the activation times of oxidation processes and the energy costs.


2018 ◽  
Author(s):  
Robert E. Smith ◽  
Bartłomiej Salamaga ◽  
Piotr Szkuta ◽  
Natalia Hajdamowicz ◽  
Tomasz K. Prajsnar ◽  
...  

AbstractEnterococcus faecalisis an opportunistic pathogen with an intrinsically high resistance to lysozyme, a key effector of the innate immune system. This high level of resistance requires several genes (oatA, pgdA, dltAandsigV) acting synergistically to inhibit both the enzymatic and cationic antimicrobial peptide activities of lysozyme. We sought to identify novel genes modulatingE. faecalisresistance to lysozyme. Random transposon mutagenesis carried out in the quadrupleoatA/pgdA/dltA/sigVmutant led to the identification of several independent insertions clustered on the chromosome. These mutations were located in a locus referred to as the enterococcal polysaccharide antigen (EPA) variable region located downstream of the highly conservedepaA-epaRgenes proposed to encode a core synthetic machinery. Theepavariable region was previously proposed to be responsible for EPA decorations, but the role of this locus remains largely unknown. Here, we show that EPA decoration contributes to resistance towards charged antimicrobials and underpins virulence in the zebrafish model of infection by conferring resistance to phagocytosis. Collectively, our results indicate that the production of the EPA rhamnopolysaccharide backbone is not sufficient to promoteE. faecalisinfections and reveal an essential role of the modification of this surface polymer for enterococcal pathogenesis.


2021 ◽  
Vol 22 (18) ◽  
pp. 9921
Author(s):  
Guang-Huey Lin ◽  
Ming-Chuan Hsieh ◽  
Hung-Yu Shu

Most bacteria possess alcohol dehydrogenase (ADH) genes (Adh genes) to mitigate alcohol toxicity, but these genes have functions beyond alcohol degradation. Previous research has shown that ADH can modulate quorum sensing in Acinetobacter baumannii, a rising opportunistic pathogen. However, the number and nature of Adh genes in A. baumannii have not yet been fully characterized. We identified seven alcohol dehydrogenases (NAD+-ADHs) from A. baumannii ATCC 19606, and examined the roles of three iron-containing ADHs, ADH3, ADH4, and ADH6. Marker-less mutation was used to generate Adh3, Adh4, and Adh6 single, double, and triple mutants. Disrupted Adh4 mutants failed to grow in ethanol-, 1-butanol-, or 1-propanol-containing mediums, and recombinant ADH4 exhibited strongest activity against ethanol. Stress resistance assays with inorganic and organic hydroperoxides showed that Adh3 and Adh6 were key to oxidative stress resistance. Virulence assays performed on the Galleria mellonella model organism revealed that Adh4 mutants had comparable virulence to wild-type, while Adh3 and Adh6 mutants had reduced virulence. The results suggest that ADH4 is primarily involved in alcohol metabolism, while ADH3 and ADH6 are key to stress resistance and virulence. Further investigation into the roles of other ADHs in A. baumannii is warranted.


2017 ◽  
Vol 14 (1) ◽  
pp. 101-112 ◽  
Author(s):  
Melissa Kelly

This article uses the concepts of ‘transnational social fields’ and ‘habitus’ to explore the multifaceted role families play in shaping the aspirations of onward migrating youth. The article draws on biographical life history interviews conducted with the children of Iranian migrants who were raised in Sweden but moved to London, UK as adults. The findings of the study suggest that from a young age, all the participants were pressured by their parents to perform well academically, and to achieve high level careers. These goals were easier to achieve in London than in Sweden for several reasons. Interestingly, however, participants’ understandings of what constituted success and their motivations for onward migration were nuanced and varied considerably by gender. The study contributes to an understanding of the role of multi-sited transnational social fields in shaping the aspirations of migrant youths, as well as the strategies taken up by these migrants to achieve their goals.


2018 ◽  
Vol 9 (01) ◽  
Author(s):  
Parul Gill ◽  
Poonam Malik ◽  
Pankaj Gill

The present study was undertaken to explore the decision making patterns of college girls in relation to clothing and their satisfaction level with these decision making patterns. Thirty under graduate college girls from Panipat city were approached to record their responses regarding decision making in relation to clothing and satisfaction level through a well structured questionnaire. It was found that most of the girls (56.66%) themselves made the decisions about the type of garment (Indian, western or both) they wear and majority of girls (70%) were highly satisfied with this decision making. Parents performed the role of buyers for their college going daughters' garments in most of the cases (63.33%) and the 73.33% girls had high level of satisfaction with this. In most of the cases (60%) the decision about the garment design was made by the girls themselves and they were highly satisfied with it. Keywords: clothing, college, girls, decision making.


Sign in / Sign up

Export Citation Format

Share Document