The Leptospiral Outer Membrane

Abstract

The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic leptospires must be able survive in both free-living and host-adapted states. As organisms move from one set of environmental conditions to another, the OM must cope with a series of conflicting challenges. For example, the OM must be porous enough to allow nutrient uptake, yet robust enough to defend the cell against noxious substances. In the host, the OM presents a surface decorated with adhesins and receptors for attaching to, and acquiring, desirable host molecules such as the complement regulator, Factor H. On the other hand, the OM must enable leptospires to evade detection by the host’s immune system on their way from sites of invasion through the bloodstream to the protected niche of the proximal tubule. The picture that is emerging of the leptospiral OM is that, while it shares many of the characteristics of the OMs of spirochetes and Gram-negative bacteria, it is also unique and different in ways that make it of general interest to microbiologists. For example, unlike most other pathogenic spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral LPS is similar to that of Gram-negative bacteria but has a number of unique structural features that may explain why it is not recognized by the LPS-specific Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major components of the leptospiral OM, though their roles are poorly understood. The functions of transmembrane OMPs in many cases are better understood thanks to homologies with their Gram-negative counterparts and the emergence of improved genetic techniques. This chapter will review recent discoveries involving the leptospiral OM and its role in leptospiral physiology and pathogenesis. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Peña Moctezuma, 2010; Cullen et al., 2004; Haake, 2000; Haake and Matsunaga, 2010; Ko et al., 2009; Raja and Natarajaseenivasan, 2013; Zuerner et al., 2000).

Expanding the paradigm for the outer membrane: Acinetobacter baumannii in the absence of endotoxin

“…1) (Moffatt et al, 2010;Beceiro et al, 2014;Boll et al, 2016). Acinetobacter joins N. meningitidis and M. catarrhalis as the three Gram-negative species viable in the absence of lipid A, excluding the genus Spirochete which have distinctive outer membranes in a class of its own (Haake and Z€ uckert, 2015). N. meningitidis was the first organism shown to survive without lipid A and LOS, which was demonstrated in 1998 when a viable lpxA mutant was generated in vitro (Steeghs et al, 1998).…”

Neuroleptospirosis: Aseptic Meningoencephalitis or Invasion into the Central Nervous System?

“…The outer membrane of leptospires is rich of lipopolysaccharides and attached with proteins for evading the hosts immune system and for penetrating tissue [6]. Electron microscopy and PCR findings in this patient's CSF proofed direct bacterial invasion of leptospires into the central nervous system.…”

“…The ability of leptospires to penetrate tissues is influenced by 12 methyl-accepting chemotaxis proteins and the spiral movements [6]. The outer membrane of leptospires is rich of lipopolysaccharides and attached with proteins for evading the hosts immune system and for penetrating tissue [6].…”

Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae

“…The candidate virulence factors for leptospiral infection include lipopolysaccharides (LPS)9, glycolipoproteins (GLP)1011, hemolysins12, adhesion molecules13, and outer membrane proteins (OMPs)1415, but their precise functions are still not completely understood. Among these factors, a 32-kDa lipoprotein, designated LipL32, is the most prominent protein in the leptospiral protein profiles and is highly conserved among pathogenic Leptospira species16.…”