All-in-one optical microfiber with an interface for MRSA in biofilms: Integrating rapid quantitative analysis and synergistic antimicrobial therapy

Abstract

The resistance and immune evasion of methicillin-resistant Staphylococcus aureus (MRSA) in biofilms are the culprits behind persistent infections. There is an urgent need for safe and effective antibacterial strategies to address MRSA and biofilm-related infections. Herein, we propose the development of an all-in-one optical microfiber that integrates rapid quantitative analysis with synergistic antimicrobial therapy for deep-seated MRSA in biofilms. The prepared interfacial-functionalized sensor can be used for quantitative analysis of MRSA in clinical whole-blood samples with low volumes (10 μL), reducing the detection time to 30 min and effectively preventing false-positive and false-negative results. The sensor can also be used for multimode antimicrobial therapy. This one-time treatment accelerates recovery and prevents recurrence through the synergistic effect of photothermal therapy, photodynamic therapy, and the antibacterial effect of Ag⁺, as well as the activation of immune memory. The therapy is localized with relatively low hyperthermia and does not cause harm to the surrounding healthy tissues. The integration of therapeutic agents onto the optical microfiber precludes their enrichment in other organs. The light guided through the optical fiber can reach deep-seated biofilms, which other light sources fail to reach. This work is promising for the clinical diagnosis and treatment of deep-seated infections.

Keywords

diagnosis and therapeutics / MRSA in biofilm / nanointerface / optical microfiber / PTT-PDT-Ag⁺

References

[1] (a) Jones KE, Patel NG, Levy MA, et al. Global trends in emerging infectious diseases. Nature. 2008; 451(7181): 990-993. (b) Taubes G. The bacteria fight back. Science. 2008; 321(5887): 356-361.

[2] Chin W, Zhong G, Pu Q, et al. A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset. Nat Commun. 2018; 9(1): 917.

[3] Oyama T, Miyazaki M, Yoshimura M, Takata T, Ohjimi H, Jimi S. Biofilm-forming methicillin-resistant Staphylococcus aureus survive in Kupffer cells and exhibit high virulence in mice. Toxins. 2016; 8(7): 198.

[4] (a) Li X, Chen D, Xie S. Current progress and prospects of organic nanoparticles against bacterial biofilm. Adv Colloid Interface Sci. 2021; 294: 102475. (b) Davies D. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov. 2003; 2(2): 114-122.

[5] (a) Centres for Disease Control and Prevention. Antibiotic Resistance Threats in the United States. US Department of Health and Human Services; 2019. (b) Qu D, Hou Z, Li J, et al. A new coumarin compound DCH combats methicillin-resistant Staphylococcus aureus biofilm by targeting arginine repressor. Sci Adv. 2020; 6: eaay9597.

[6] Hogan PG, Mork RL, Thompson RM, et al. Environmental methicillin-resistant Staphylococcus aureus contamination, persistent colonization, and subsequent skin and soft tissue infection. JAMA Pediatr. 2020; 174(6): 552.

[7] Zhang A, Wu H, Chen X, et al. Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms. Sci Adv. 2023; 9(28): eadg9116.

[8] Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399(10325): 629-655.

[9] Cheng Y, Zhang Y, Zhao Z, et al. Guanidinium-decorated nanostructure for precision sonodynamic-catalytic therapy of MRSA-infected osteomyelitis. Adv Mater. 2022; 34(50): 2206646.

[10] (a) Celik C, Ildiz N, Sagiroglu P, Atalay MA, Yazici C, Ocsoy I. Preparation of nature inspired indicator based agar for detection and identification of MRSA and MRSE. Talanta. 2020; 219: 121292. (b) Sharaf MH, El-Sherbiny GM, Moghannem SA, et al. New combination approaches to combat methicillinresistant Staphylococcus aureus (MRSA). Sci Rep. 2021; 11(1): 4240.

[11] (a) Schulz M, Calabrese S, Hausladen F, et al. Point-of-care testing system for digital single cell detection of MRSA directly from nasal swabs. Lab Chip. 2020; 20(14): 2549-2561. (b) Choopara I, Suea-Ngam A, Teethaisong Y, et al. Fluorometric paper-based, loop-mediated isothermal amplification devices for quantitative point-of-care detection of methicillinresistant Staphylococcus aureus (MRSA). ACS Sens. 2021; 6(3): 742-751. (c) Yi Y, Han Y, Cheng X, et al. Three-dimensional surface-enhanced Raman scattering platform with hotspots built by a nano-mower for rapid detection of MRSA. Anal Chem. 2022; 94(49): 17205-17211. (d) Peng R, Chen X, Xu F, Hailstone R, Men Y, Du K. Pneumatic nano-sieve for CRISPRbased detection of drug-resistant bacteria. Nanoscale Horiz. 2023; 8(12): 1677-1685.

[12] Srivastava K, Bozic KJ, Silverton C, Nelson AJ, Makhni EC, Davis JJ. Reconsidering strategies for managing chronic periprosthetic joint infection in Total knee arthroplasty. J Bone Joint Surg. 2019; 101(1): 14-24.

[13] (a) Li J, Liu X, Tan L, et al. Zinc-doped Prussian blue enhances photothermal clearance of Staphylococcus aureus and promotes tissue repair in infected wounds. Nat Commun. 2019; 10(1): 4490. (b) Tang H, Qu X, Zhang W, et al. Photosensitizer nanodot eliciting immunogenicity for photoimmunologic therapy of postoperative methicillin-resistant Staphylococcus aureus infection and secondary recurrence. Adv Mater. 2022; 34(12): 2107300. (c) Yang L, Zhang D, Li W, et al. Biofilm microenvironment triggered self-enhancing photodynamic immunomodulatory microneedle for diabetic wound therapy. Nat Commun. 2023; 14(1): 7658. (d) Tang J, Chu B, Wang J, et al. Multifunctional nanoagents for ultrasensitive imaging and photoactive killing of gramnegative and gram-positive bacteria. Nat Commun. 2019; 10(1): 4057.

[14] (a) Tabassum S, Kumar R. Advances in fiber-optic technology for point-of-care diagnosis and in vivo biosensing. Adv Mater Technol. 2020; 5(5): 1900792. (b) Lobry M, Loyez M, Debliquy M, Chah K, Goormaghtigh E, Caucheteur C. Electro-plasmonic-assisted biosensing of proteins and cells at the surface of optical fiber. Biosens Bioelectron. 2023; 220: 114867. (c) Liang H, Zhou L, Chen P, et al. Optical microfiber with a gold nanorods–black phosphorous nanointerface: an ultrasensitive biosensor and nanotherapy platform. Anal Chem. 2022; 94(22): 8058-8065. (d) Cui W, Xiao A, Luo C, et al. Bimetallic interface on an optical microfiber nucleic acid sensor: early detection in body fluids. Chem Eng J. 2024; 490: 151376.

[15] (a) Guan BO, Huang Y. Interface sensitized optical microfiber biosensors. J Lightwave Technol. 2019; 37(11): 2616-2622. (b) Xiao A, Huang Y, Zheng J, Chen P, Guan B-O. An optical microfiber biosensor for CEACAM5 detection in serum: sensitization by a nanosphere interface. ACS Appl Mater Interfaces. 2020; 12(1): 1799-1805. (c) Chen P, Huang Y, Bo Y, Liang H, Xiao A, Guan B-O. 3D nanointerface enhanced optical microfiber for real-time detection and sizing of single nanoparticles. Chem Eng J. 2021; 407: 127143.

[16] Chen P, Wu H, Zhao Y, et al. Quantitative assessment of fungal biomarkers in clinical samples via an interface-modulated optical fiber biosensor. Adv Mater. 2024; 36(21): 2312985.

[17] (a) Xiao A, Zheng J, Wu X, et al. Ultrasensitive detection and cellular photothermal therapy via a self-photothermal modulation biosensor. Adv Opt Mater. 2023; 11(8): 2202711. (b) Wu H, Chen P, Zhan X, et al. Marriage of a dual-plasmonic interface and optical microfiber for NIR-II cancer theranostics. Adv Mater. 2024; 36 (8): 2310571.

[18] Zhang J, Fang H, Wang P, et al. Optical microfiber or nanofiber: a miniature fiber-optic platform for nanophotonics. Photon Insights. 2024; 3: R02.

[19] Huang Y, Liang J, Chen P, et al. Fiber-optic microfiber: tracking activity enhancement and suppression of heterogeneous photocatalysts. Adv Fiber Mater. 2023; 5(2): 527-542.

[20] Tong L, Gattass RR, Ashcom JB, et al. Subwavelength-diameter silica wires for low-loss optical wave guiding. Nature. 2003; 426(6968): 816-819.

[21] (a) Alqarni SA, Willmore WG, Albert J, Smelser CW. Self-monitored and optically powered fiber-optic device for localized hyperthermia and controlled cell death in vitro. Appl Optics. 2021; 60(8): 2400. (b) Ran Y, Xu Z, Chen M, et al. Fiberoptic theranostics (FOT): interstitial fiber-optic needles for cancer sensing and therapy. Adv Sci. 2022; 9(15): 2200456.

[22] Li H, Huang Y, Chen C, et al. Real-time cellular cytochrome C monitoring through an optical microfiber: enabled by a silver-decorated graphene nanointerface. Adv Sci. 2018; 5(8): 1701074.

[23] Eigler S, Hof F, Enzelberger-Heim M, Grimm S, Müller P, Hirsch A. Statistical Raman microscopy and atomic force microscopy on heterogeneous graphene obtained after reduction of graphene oxide. J Phys Chem C. 2014; 118(14): 7698-7704.

[24] Lou J, Wang Y, Tong L. Microfiber optical sensors: a review. Sensors. 2014; 14(4): 5823-5844.

[25] Fu Y, Wang N, Yang A, Law H K-w, Li L, Yan F. Highly sensitive detection of protein biomarkers with organic electrochemical transistors. Adv Mater. 2017; 29(41): 1703787.

[26] (a) Li Y, Tang X, Wang N, et al. Argonaute-DNAzyme tandem biosensing for highly sensitive and simultaneous dual-gene detection of methicillin-resistant Staphylococcus aureus. Biosens Bioelectron. 2024; 244: 115758. (b) Song D, Xu W, Han X, et al. CRISPR/Cas12a-powered evanescent wave fluorescence nanobiosensing platform for nucleic acid amplification-free detection of Staphylococcus aureus with multiple signal enhancements. Biosens Bioelectron. 2023; 225: 115109. (c) Nguyen TT-Q, Gu MB. An ultrasensitive electrochemical aptasensor using Tyramide-assisted enzyme multiplication for the detection of Staphylococcus aureus. Biosens Bioelectron. 2023; 228: 115199.

[27] Li H, Huang Y, Hou G, et al. Single-molecule detection of biomarker and localized cellular photothermal therapy using an optical microfiber with nanointerface. Sci Adv. 2019; 5(12): eaax4659.

[28] Sun Y, Liu M, Sun W, et al. A hemoglobin bionics-based system for combating antibiotic resistance in chronic diabetic wounds via iron homeostasis regulation. Adv Mater. 2024; 36(30): 2405002.

[29] Ding L, Liang X, Ma J, et al. Sono-triggered biomimetically nanoantibiotics mediate precise sequential therapy of MRSA-induced lung infection. Adv Mater. 2024; 36 (46): 2403612.

[30] Hughes G, Webber MA. Novel approaches to the treatment of bacterial biofilm infections. Br J Pharmacol. 2017; 174(14): 2237-2246.

[31] Tan S, Wu X, Xing Y, Lilak S, Wu M, Zhao J. Enhanced synergetic antibacterial activity by a reduce graphene oxide/Ag nanocomposite through the photothermal effect. Colloids Surf B Biointerfaces. 2020; 185: 110616.

[32] Morones-Ramirez JR, Winker JA, Spina CS, Collins JJ. Silver enhances antibiotic activity against gram-negative bacteria. Sci Transl Med. 2013; 5(190): 190ra81.

[33] Mei Z, Gao D, Hu D, et al. Activatable NIR-II photoacoustic imaging and photochemical synergistic therapy of MRSA infections using miniature Au/Ag nanorods. Biomaterials. 2020; 251: 120092.

[34] Vaish M, Price-Whelan A, Reyes-Robles T, et al. Roles of Staphylococcus aureus Mnh1 and Mnh2 Antiporters in Salt Tolerance, Alkali Tolerance, and Pathogenesis. J Bacteriol. 2018; 200: 5.

[35] Xue L, Chen YY, Yan Z, Lu W, Wan D, Zhu H. Staphyloxanthin: a potential target for antivirulence therapy. Infect Drug Resist. 2019; 12: 2151-2160.

[36] Huang Y, Liang J, Wu H, Chen P, Xiao A, Guan B. Microscale insight into the proton concentration during electrolytic reaction via an optical microfiber: potential for microcurrent monitoring by a dielectric probe. Light Sci Appl. 2025; 14(1): 73.

[37] Hamidreza K, Alireza T, Mohammad Hassan M, Mohammad Hosein P, Mohammad K. Fabrication of low-loss adiabatic optical microfibers using an attainable arc-discharge fiber tapering setup. Opt Commun. 2022; 522: 128669.

[38] Kordi F, Khorsand Zak A, Darroudi M, Hazrati Saedabadi M. Synthesis and characterizations of Ag-decorated graphene oxide nanosheets and their cytotoxicity studies. Chem Pap. 2019; 73(8): 1945-1952.

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