Leptospira: a spirochaete with a hybrid outer membrane

Abstract

Leptospira is a genus of spirochaetes that includes organisms with a variety of lifestyles ranging from aquatic saprophytes to invasive pathogens. Adaptation to a wide variety of environmental conditions has required leptospires to acquire a large genome and a complex outer membrane with features that are unique among bacteria. The most abundant surface-exposed outer membrane proteins are lipoproteins that are integrated into the lipid bilayer by amino-terminal fatty acids. In contrast to many spirochaetes, the leptospiral outer membrane also includes lipopolysaccharide and many homologues of well-known beta-barrel transmembrane outer membrane proteins. Research on leptospiral transmembrane outer membrane proteins has lagged behind studies of lipoproteins because of their aberrant behaviour by Triton X-114 detergent fractionation. For this reason, transmembrane outer membrane proteins are best characterized by assessing membrane integration and surface exposure. Not surprisingly, some outer membrane proteins that mediate host-pathogen interactions are strongly regulated by conditions found in mammalian host tissues. For example, the leptospiral immunoglobulin-like (Lig) repeat proteins are dramatically induced by osmolarity and mediate interactions with host extracellular matrix proteins. Development of molecular genetic tools are making it possible to finally understand the roles of these and other outer membrane proteins in mechanisms of leptospiral pathogenesis.

Fig. 1

Leptospiral membrane architecture. The leptospiral outer membrane contains a mixture of lipopolysaccharide, surface-exposed lipoproteins, and transmembrane proteins. The most abundant outer membrane lipoproteins are LipL32 and Loa22. Loa22 may contain a novel transmembrane segment connecting its surface-exposed and periplasmic peptidoglycan binding domains. Periplasmic flagella (PF) are located in the periplasm. FecA is a TonB-dependent receptor for ferric citrate and aerobactin. TolC forms an efflux channel with ATPase pumps in the cytoplasmic membrane.