Gram-negative bacterial cell membrane glycans and proteins

The Gram-negative bacterial cell membrane is a complex structure characterized by an outer membrane containing lipopolysaccharides (LPS), various glycans, and integral outer membrane proteins (OMPs). This surface serves as a critical barrier against environmental threats and host immune defenses, while also facilitating nutrient transport and cell signaling. In the context of immunotherapy, these surface components are targeted by bifunctional antibody-recruiting molecules (ARMs) or Alphamers. These therapeutic agents consist of a targeting domain that binds to bacterial membrane glycans or proteins and an effector domain that recruits endogenous host antibodies, such as polyclonal IgG or anti-alpha-Gal antibodies. By coating the bacterial surface with host antibodies, these drugs trigger potent immune effector mechanisms, including complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP), leading to the rapid clearance of even multidrug-resistant (MDR) pathogens.

Other names

Gram-negative bacterial cell envelopeGram-negative outer membraneLipopolysaccharide (LPS)Outer membrane proteins (OMPs)Bacterial surface glycans

Recruitment of endogenous host antibodies (e.g., anti-alpha-Gal IgG) to the bacterial surface to induce opsonization, complement activation, and phagocytosis.