Shaping Gram-negative bacterial phenotypes
Antibodies and other immune effectors are crucial for protecting humans from Gram-negative bacteria. Antibodies can bind outer membrane or cell surface (e.g. flagella) structures, thereby preventing adhesion, disrupting specific virulence functions, or targeting bacteria for phagocytosis. Immune effectors (antimicrobial peptides, cytokines and hormones) impinge on bacterial infections and regulate immune responses. A developing paradigm is that bacteria ‘recognize’ antibodies and immune effectors, which alert them to challenging environments, promoting resistance phenotypes and increased virulence. A broader understanding of the interactions between bacteria and antibodies and immune effectors will help define their relative contributions to pathogenesis, and perhaps indicate how we could use antibodies and immune effectors to shape bacterial phenotypes that are easier for the immune system to control.
Systems biologists use data sets from microarray (transcription networks) and yeast two-hybrid interaction (protein–protein networks) screens to define interactors in the network. A long-term goal is to understand the networks on which outer membrane structures impinge, and how to regulate them to positive effect. The challenge then becomes how to advance this perspective to develop therapeutic strategies. Currently, discovery of the protective roles of antibodies needs to be expanded from individual outer membranes of isolated bacteria. The breadth of regulation by different outer membrane-specific antibodies needs to be uncovered so bacterial phenotypes can be shaped and exploited. The current trend to antibiotic resistance indicates a need for alternative therapies that might be filled by outer membrane-specific antibodies and other immune effectors.