Antibody–Antimicrobial Conjugates for Combating Antibiotic Resistance

Abstract

As the development of new antibiotics lags far behind the emergence of drug-resistant bacteria, alternative strategies to resolve this dilemma are urgently required. Antibody-drug conjugate is a promising therapeutic platform to delivering cytotoxic payloads precisely to target cells for efficient disease treatment. Antibody-antimicrobial conjugates (AACs) have recently attracted considerable interest from researchers as they can target bacteria in the target sites and improve the effectiveness of drugs (i.e., reduced drug dosage and adverse effects), abating the upsurge of antimicrobial resistance. In this review, the selection and progress of three essential blocks that compose the AACs: antibodies, antimicrobial payloads, and linkers are discussed. The commonly used conjugation strategies and the latest applications of AACs in recent years are also summarized. The challenges and opportunities of this booming technology are also discussed at the end of this review.

Antibody‐Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

“…[ 38 ] Enhanced deliverable payload can be achieved using tools of nanomedicine, such as liposomes or solid nanoparticles, [ 10 , 39 ] whereas enzymes and nanozymes may prove useful for localized drug synthesis schemes. [ 12 , 40 ] Each of these techniques has its own merits. ADCs have a competitive edge in that multiple products are already on the market and numerous candidates navigate through clinical trials, illustrating that technology for the production of ADC is well‐established, and clinical acceptance of these agents is very high.…”

“…[ 11 ] Finally, with relevance to this work, antimicrobial measures can employ prodrug therapies where an inactive drug is circulating in the body and only activated at site of infection. [ 12 ] In the latter case, promising results have very recently been obtained when prodrug activation was mediated by the host enzymes (typically proteases). [ 13 ] In this study, we take advantage of drug repurposing and prodrug therapy to deliver an anti‐neoplastic drug that is highly effective against biofilms and will benefit from a prodrug therapy approach to minimize side effects.…”

“…Examples of the use of ADC for the treatment of bacterial diseases (also termed antibody‐antibiotic conjugates, AAC) are scant. [ 12 , 17 ] In large part, this is because bacteria do not perform receptor‐mediated endocytosis, and methods should be designed to achieve drug release without the prodrug entry into the bacterial cells. In one successful example, an ADC has been developed to bind a bacterium and through opsonization to facilitate the uptake of the pathogen by the immune cells.…”

Strategies for the eradication of intracellular bacterial pathogens

“…Inspired by the recent success in the development of antibody-drug conjugates (ADCs) for cancer treatment, 136 one attractive therapeutic approach with the potential to treat bacterial infections is the development of antibody-antibiotic conjugates (AACs), 25,[137][138][139][140][141][142] which combines the key attributes of both the antibody and the antibiotic in one single molecule. Specifically, AACs possess the antibacterial activity of antibiotics, and the specificity and high affinity of antibodies.…”

Antibody–Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections

“…By specifically targeting bacteria and delivering antibiotics directly to the site of infection, AACs can improve the effectiveness of drugs while reducing the selection pressure of antibiotics [3]. This targeted approach may help overcome resistance and reduce adverse effects associated with high drug dosages [48].…”