Antibacterial activity of iron oxide, iron nitride, and tobramycin conjugated nanoparticles against Pseudomonas aeruginosa biofilms

被引:116
作者
Armijo, Leisha M. [1 ]
Wawrzyniec, Stephen J. [1 ]
Kopciuch, Michael [1 ]
Brandt, Yekaterina I. [1 ]
Rivera, Antonio C. [1 ]
Withers, Nathan J. [1 ]
Cook, Nathaniel C. [1 ]
Huber, Dale L. [2 ]
Monson, Todd C. [3 ]
Smyth, Hugh D. C. [4 ]
Osinski, Marek [1 ]
机构
[1] Univ New Mexico, Ctr High Technol Mat, 1313 Goddard St SE, Albuquerque, NM 87106 USA
[2] Sandia Natl Labs, Ctr Integrated Nanotechnol, 1000 Eubank SE, Albuquerque, NM 87123 USA
[3] Sandia Natl Labs, Nanomat Sci, POB 5800,MS 1415, Albuquerque, NM 87185 USA
[4] Univ Texas Austin, Coll Pharm, 2409 Univ Ave,Stop A1900, Austin, TX 78712 USA
基金
美国国家卫生研究院;
关键词
Antibiotic resistance; Pseudomonas aeruginosa; Cystic fibrosis; Biofilm; Antibacterial agents; Drug delivery; Iron-oxide nanoparticles; Zero-valent iron nanoparticles; Magnetite; Alginate; VENTILATOR-ASSOCIATED PNEUMONIA; EXTENSIVELY DRUG-RESISTANT; SILVER NANOPARTICLES; MULTIDRUG-RESISTANT; NOSOCOMIAL INFECTIONS; FE3O4; NANOPARTICLES; BACTERIAL BIOFILMS; INHALATION POWDER; ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE;
D O I
10.1186/s12951-020-0588-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method for P. aeruginosa infection still eludes investigators, despite the extensive research in this area. Results We report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of 16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to 230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of 232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies. Conclusions Positive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite-tobramycin conjugates inhibit P. aeruginosa growth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.
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页数:27
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