Bacterial infections are an increasing global health concern, driven by the dual threat of antibiotic resistance and bacterial strategies to evade the host immune system. Increased antibiotic resistance is expected to cause 10 million deaths annually by 2050 [1], calling for the development of novel antibacterial agents. Additionally, elimination of pathogenic bacteria within the host is impeded by immune evasion strategies of bacteria, including neutralizing toxic host molecules, escaping cellular destruction, and altering antigenic epitopes to antibody-mediated immune recognition [2]. Given the rapid emergence of antibiotic-resistant bacteria, the gap in the development of new antibiotics, and the evolution of bacteria to subvert host effector functions, there is an urgent need for novel therapeutic strategies.

Immunotherapy, which enhances the body’s immune system to fight diseases, including bacterial infections, involves several modalities such as monoclonal antibodies, vaccines, T-cell therapies, cytokine modulation, and immune checkpoint inhibitors [3]. Among emerging immunotherapeutic approaches, antibody-recruiting molecules (ARMs) are gaining traction as a strategy to target bacterial infections. ARMs are bispecific small molecules that graft haptens onto target cell surfaces, which leads to recruitment of anti-hapten antibodies, engagement of immune cells and the complement system, and ultimately enhanced clearance of pathogenic cells [4]. Although ARM technology is still relatively nascent, examples of ARMs targeting cancer [5, 6, 7, 8, 9], fungi [10], and viruses [11,12] have been reported, with an ongoing phase 1 clinical trial on multiple myeloma patients using a CD38-specific ARM [13]. Prior review articles have broadly covered the ARM concept and its applications to targeting different diseases [4,14, 15, 16, 17, 18], including one focused on bacteria published in 2018 [19]. Here, we review ARM strategies developed for combating bacteria, briefly revisiting seminal work and emphasizing recent advances using ARMs to target Gram-positive bacteria, Gram-negative bacteria, and mycobacteria.