Influences of strains and environment conditions on lipid A: A case study of Francisella

Tularemia is a zoonosis caused by gram-negative bacteria Francisella tularensis, which has LPS in outer membrane. Lipid A is the most conservative part in LPS and is important for LPS function of bacteria survival and host immune response stimulation. For a certain strain, the lipid A structure is unique, but can also influenced by different environmental conditions. The mechanisms of how lipid A synthesis and modification changes will affect immune mechanism still remain many questions. This article briefly introduces the enzymes participating general lipid A synthesis process. F. novicida, as a specific example, has differences in lipid A-related enzymes from those of ordinary bacteria. Lipid A structure and content can be regulated by some environment conditions like temperature differences between environment and host cells. The structure of lipid A determines its function, so bacterial virulence is various. Some F. novicida knockout mutants have no ability to stimulate immune response in host cells and have lower toxicity than wild-type strains. In therapy, modified lipid A is used as immune adjuvant and some lipid A mutant strains can be vaccines to protect animals against lethal Francisella strain infection. A deeper understanding of Francisella lipid A structure, regulation and immune mechanisms helps to prevent and treat tularemia disease. In future research, more enzymes affecting characteristics of lipid A or the whole LPS can be further studied. More effective vaccines and drug design relies on a better understanding of pathogenic mechanisms.