Fighting Staphylococcus aureus infections with light and photoimmunoconjugates

Abstract

Conflict of interest: KPF reports that he is an employee of PerkinElmer Inc., the manufacturer of optical and PET imaging equipment. GMVD is CEO, founder, and shareholder of AxelaRx/ TRACER group and CSO AxelaRx Biosciences Inc. JMVD has filed a patent application on the use of 1D9 (US 9,944,694 B2), which is owned by his employer University Medical Center Groningen.

Redirected Stress Responses in a Genome-Minimized ‘midi Bacillus ’ Strain with Enhanced Capacity for Protein Secretion

“…However, there is currently no vaccine against MRSA infections, and the search for suitable staphylococcal antigens for vaccination is still in progress ( 23 , 24 ). Importantly, the model protein IsaA employed in our present study to asses protein secretion by midi Bacillus is a potential target for innovative antistaphylococcal immunotherapy ( 25 – 27 ).…”

Monoclonal Antibodies Targeting Surface-Exposed and Secreted Proteins from Staphylococci

“…Besides the use of mAbs in passive immunization, the development of antibody-conjugated antibacterial agents may have beneficial effects against staphylococcal infections. For example, the development of antibodyantibiotic conjugates proved highly effective in combating bacteria restricted to intracellular compartments [ 120 , 121 ]. The application of this platform might be potentially extended to staphylococcal biofilm or to bacteria localized in specific niches of the body where the binding of an antibody to a particular antigen concentrates the antibiotic and increases its effectiveness.…”

“…The resulting immunoconjugate 1D9-IRDye700DX, when activated by illumination with red light, induced generation of ROS and the consequent disruption of S. aureus biofilms in vitro and rescued larvae of the wax moth Galleria mellonella from staphylococcal infections. Moreover, the immunoconjugate proved effective in the killing of S. aureus in a human postmortem infection model [ 121 ]. Likewise, gold nanoparticles conjugated to monoclonal antibodies specific to S. aureus peptidoglycan, when incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus and activated by pulsed laser irradiation, significantly reduced bacterial viability thanks to photothermal killing [ 122 ].…”

Targeted Antimicrobial Photodynamic Therapy of Biofilm-Embedded and Intracellular Staphylococci with a Phage Endolysin’s Cell Binding Domain

“…Ideally, the photosensitizer should be coupled to a targeting agent to achieve higher specificity and efficacy. We previously developed an immunoconjugate based on a S. aureus -specific human monoclonal antibody and the photosensitizer IRDye 700DX ( 12 ). This immunoconjugate was capable of killing planktonic and biofilm-embedded S. aureus , showing in vivo efficacy with minimal cytotoxic side effects toward mammalian cells ( 12 ).…”

“…We previously developed an immunoconjugate based on a S. aureus -specific human monoclonal antibody and the photosensitizer IRDye 700DX ( 12 ). This immunoconjugate was capable of killing planktonic and biofilm-embedded S. aureus , showing in vivo efficacy with minimal cytotoxic side effects toward mammalian cells ( 12 ). However, the Achilles heel of monoclonal antibodies is that they address only one specific target epitope.…”