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Mild magnetic nanoparticle hyperthermia enhances the susceptibility of Staphylococcus aureus biofilm to antibiotics.

ABSTRACT: Objective: A critical challenge in the treatment of biofilm infection is the capacity of biofilm-grown bacteria to develop resistance to traditional antimicrobial therapies. The objective of this study was to validate the therapeutic potential of magnetic nanoparticle/alternating magnetic field (MNP/AMF) hyperthermia in combination with conventional antibiotics against biofilm infection.Materials and methods: The impact of MNP/AMF hyperthermia on the viability of S. aureus biofilm in the absence and presence of antibiotics as well as on the bactericidal activity of macrophages were evaluated at varying conditions of MNPs concentration and AMF intensity using in vitro cell culture models.Results: The application of MNP/AMF alone at a CEM43 thermal dose below the threshold for skin tissue exhibited a modest efficacy in the eradication of Staphylococcus aureus (S. aureus) biofilm (<1-log reduction). The treatment of antibiotics (ciprofloxacin, vancomycin) alone at a bactericidal concentration for planktonic S. aureus had no significant effect on the eradication of biofilm phase of S. aureus. However, when the biofilm was pre-exposed to mild MNP/AMF hyperthermia, the treatment of antibiotics could exhibit bactericidal effects against S. aureus biofilm, which was associated with increased uptake of antibiotics to the bacterial cells. Importantly, the application of MNP/AMF could promote the bactericidal activity of macrophages against intracellular bacteria via MNP-dependent generation of reactive oxygen species (ROS).Conclusion: Our results validate that the application of mild MNP/AMF hyperthermia within a safe thermal dose threshold is synergistic with conventional antibiotics as well as aids host innate immune response of macrophages for the clearance of intracellular bacteria.

SUBMITTER: Alumutairi L

PROVIDER: S-EPMC7730973 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mild magnetic nanoparticle hyperthermia enhances the susceptibility of Staphylococcus aureus biofilm to antibiotics.

Alumutairi Layla L Yu Bing B Filka Mitchell M Nayfach Joseph J Kim Min-Ho MH

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 20200101 1

Objective: A critical challenge in the treatment of biofilm infection is the capacity of biofilm-grown bacteria to develop resistance to traditional antimicrobial therapies. The objective of this study was to validate the therapeutic potential of magnetic nanoparticle/alternating magnetic field (MNP/AMF) hyperthermia in combination with conventional antibiotics against biofilm infection.Materials and methods: The impact of MNP/AMF hyperthermia on the viability of S. aureus biofilm ...[more]

PMID: 31964196

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Project description:Effective antimicrobials are crucial for managing Staphylococcus aureus implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant S. aureus (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial Staphylococcal bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (106 PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (106 PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches.

Project description:Staphylococcus aureus is a frequent cause of ocular surface infections worldwide. Of these surface infections, those involving the cornea (microbial keratitis) are most sight-threatening. S. aureus can also cause conjunctivitis and contact lens-related non-infectious corneal infiltrative events (niCIE). The aim of this study was to determine the rates of resistance of S. aureus isolates to antibiotics and disinfecting solutions from these different ocular surface conditions. In total, 63 S. aureus strains from the USA and Australia were evaluated; 14 were from niCIE, 26 from conjunctivitis, and 23 from microbial keratitis (MK). The minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of all the strains to ciprofloxacin, ceftazidime, oxacillin, gentamicin, vancomycin, chloramphenicol, azithromycin, and polymyxin B were determined. The MIC and MBC of the niCIE strains to contact lens multipurpose disinfectant solutions (MPDSs) was determined. All isolates were susceptible to vancomycin (100%). The susceptibility to other antibiotics decreased in the following order: gentamicin (98%), chloramphenicol (76%), oxacillin (74%), ciprofloxacin (46%), ceftazidime (11%), azithromycin (8%), and polymyxin B (8%). In total, 87% of all the isolates were multidrug resistant and 17% of the isolates from microbial keratitis were extensively drug resistant. The microbial keratitis strains from Australia were usually susceptible to ciprofloxacin (57% vs. 11%; p = 0.04) and oxacillin (93% vs. 11%; p = 0.02) compared to microbial keratitis isolates from the USA. Microbial keratitis isolates from the USA were less susceptible (55%) to chloramphenicol compared to conjunctivitis strains (95%; p = 0.01). Similarly, 75% of conjunctivitis strains from Australia were susceptible to chloramphenicol compared to 14% of microbial keratitis strains (p = 0.04). Most (93%) strains isolated from contact lens wearers were killed in 100% MPDS, except S. aureus 27. OPTI-FREE PureMoist was the most active MPDS against all strains with 35% of strains having an MIC ≤ 11.36%. There was a significant difference in susceptibility between OPTI-FREE PureMoist and Biotrue (p = 0.02). S. aureus non-infectious CIE strains were more susceptible to antibiotics than conjunctivitis strains and conjunctivitis strains were more susceptible than microbial keratitis strains. Microbial keratitis strains from Australia (isolated between 2006 and 2018) were more susceptible to antibiotics in comparison with microbial keratitis strains from the USA (isolated in 2004). Most of the strains were multidrug-resistant. There was variability in the susceptibility of contact lens isolates to MPDSs with one S. aureus strain, S. aureus 27, isolated from niCIE, in Australia in 1997 being highly resistant to all four MPDSs and three different types of antibiotics. Knowledge of the rates of resistance to antibiotics in different conditions and regions could help guide treatment of these diseases.

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Mild magnetic nanoparticle hyperthermia enhances the susceptibility of Staphylococcus aureus biofilm to antibiotics.

Publications

Mild magnetic nanoparticle hyperthermia enhances the susceptibility of <i>Staphylococcus aureus</i> biofilm to antibiotics.

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