9bc21942dc17125c3d1d6297e2e0c28c pmc_10269648.pdf 6e6fece504dfdd9bfd86936e811a0d4ca2f73c8a pmc_10269648.pdf b9fd27bc40fb68701de30053c1552ce77d174e78fe51ffedd2a2724115a07905 pmc_10269648.pdf Title: In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains Subject: Research Article Keywords: antibacterial activity; MDR/XDR; amikacin; biofilms; hyperthermia; silver nanoparticles Author: Marta Palau;Estela Muñoz;Muriel F. Gusta;Nieves Larrosa;Xavier Gomis;Joan Gilabert;Benito Almirante;Victor Puntes;Robert Texidó;Joan Gavaldà Creator: PTC Arbortext Advanced Print Publisher 11.1.4012/W Producer: Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version) CreationDate: Fri Jun 2 13:33:13 2023 CEST ModDate: Mon Jun 5 13:07:21 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 584.957 x 782.986 pts Page rot: 0 File size: 3328258 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ALHFME+AdvOT56309c18.I Type 1C WinAnsi yes yes no 479 0 ALHFMF+AdvOTce3d9a73 Type 1C WinAnsi yes yes no 109 0 ALHFMG+AdvOTce3d9a73+fb Type 1C Custom yes yes yes 480 0 ALHGBF+AdvOT07517017 Type 1C WinAnsi yes yes no 481 0 ALHGBG+AdvOT07517017+20 Type 1C WinAnsi yes yes no 482 0 ALHGBH+AdvOT3b30f6db.B Type 1C WinAnsi yes yes no 44 0 ALHGBI+AdvOT46dcae81 Type 1C WinAnsi yes yes no 45 0 ALHGBJ+AdvOT46dcae81+fb Type 1C Custom yes yes yes 46 0 ALHGBK+AdvOT65f8a23b.I Type 1C WinAnsi yes yes no 47 0 ALHGBL+AdvOT07517017+fb Type 1C Custom yes yes yes 483 0 ALHGEL+AdvOT46dcae81+20 Type 1C WinAnsi yes yes no 48 0 ALHGFM+AdvPSUnvGMP Type 1C WinAnsi yes yes no 81 0 ALHGFN+AdvP80675 Type 1C WinAnsi yes yes no 82 0 ALHGGN+AdvP4C4E74 Type 1C Custom yes yes no 88 0 ALHGLM+AdvOT3b30f6db.B+fb Type 1C Custom yes yes yes 110 0 ALHGLN+AdvOT8817665d Type 1C WinAnsi yes yes no 111 0 ALHGLO+AdvOT153e3c55.B Type 1C WinAnsi yes yes no 106 0 ALHJCP+AdvOTb214af43 Type 1C WinAnsi yes yes no 160 0 ALHJEA+AdvP7DA6 Type 1C WinAnsi yes yes no 191 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-21 02:32:13 CEST RepresentationInformation: pmc_10269648.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-10-11 02:19:59 CEST Size: 3328258 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - 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Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Characterization of AgNPs_mPEG and AgNPs_mPEG_AK. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Planktonic susceptibility studies. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: (ii) Efficacy of AgNPs_mPEG, AgNPs_mPEG_AK, AgNPs_mPEG plus AK, and AK alone over time. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: (iii) Efficacy of AgNPs_mPEG_AK and hyperthermia. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Biofilm susceptibility studies: efficacy of AgNPs_mPEG_AK and hyperthermia determined by CLSM. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: DISCUSSION Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: MATERIALS AND METHODS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Children: Item: Title: Strains and resistance mechanisms. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Antimicrobial agents. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Planktonic susceptibility studies. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: Biofilm susceptibility studies. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: ACKNOWLEDGMENTS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: REFERENCES Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Info: Title: In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains Author: Marta Palau;Estela Muñoz;Muriel F. Gusta;Nieves Larrosa;Xavier Gomis;Joan Gilabert;Benito Almirante;Victor Puntes;Robert Texidó;Joan Gavaldà Subject: Research Article Keywords: antibacterial activity; MDR/XDR; amikacin; biofilms; hyperthermia; silver nanoparticles Creator: PTC Arbortext Advanced Print Publisher 11.1.4012/W Producer: Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version) CreationDate: Fri Jun 02 14:03:13 CEST 2023 ModDate: Mon Jun 05 13:37:21 CEST 2023 ID: 0x66004e910600205dd16e8eebe0a158ba, 0xc275a4a40c16d2b698d5b3159b4b906f Filters: FilterPipeline: FlateDecode Images: Image: NisoImageMetadata: FormatName: image/png ImageWidth: 67 ImageHeight: 67 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Fonts: Type1: Font: BaseFont: ALHFMG+AdvOTce3d9a73+fb FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: ALHFMG+AdvOTce3d9a73+fb Flags: Symbolic FontBBox: 0, 0, 795, 721 FontFile3: true EncodingDictionary: Differences: true ToUnicode: 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FontBBox: -20, -208, 1000, 770 FontFile3: true Encoding: WinAnsiEncoding XMP: In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains 10.1128/spectrum.00280-23 Marta Palau Estela Muñoz Muriel F. Gusta Nieves Larrosa Xavier Gomis Joan Gilabert Benito Almirante Victor Puntes Robert Texidó Joan Gavaldà Research Article Research Article antibacterial activity MDR/XDR amikacin biofilms hyperthermia silver nanoparticles American Society for Microbiology Palau et al. Copyright © 2023 Palau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 20230420 2023 ABSTRACT In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections. 20230117 20230331 2165-0497 Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 50, 565, 97, 574 Annotation: Subtype: Link Rect: 122, 565, 173, 574 Annotation: Subtype: Link Rect: 181, 554, 233, 563 Annotation: Subtype: Link Rect: 410, 124, 506, 131 Annotation: Subtype: Link Rect: 400, 115, 456, 122 Annotation: Subtype: Link Rect: 444, 24, 526, 31 Annotation: Subtype: Link Rect: 508, 683, 544, 719 Page: Label: 2 Annotations: Annotation: Subtype: Link Rect: 221, 570, 226, 579 Destination: 239 Annotation: Subtype: Link Rect: 230, 570, 235, 579 Destination: 239 Annotation: Subtype: Link Rect: 223, 546, 227, 554 Destination: 239 Annotation: Subtype: Link Rect: 233, 546, 237, 554 Destination: 239 Annotation: Subtype: Link Rect: 64, 521, 69, 530 Destination: null Annotation: Subtype: Link Rect: 164, 509, 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