The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis

doi:10.1016/j.ijmm.2004.01.003

International Journal of Medical Microbiology

Volume 294, Issue 1, 28 June 2004, Pages 7-14

https://doi.org/10.1016/j.ijmm.2004.01.003 Get rights and content

Abstract

The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved β-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease α2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression.

Section snippets

Introduction: the omptin family

The omptins are a family of outer membrane proteases that have been identified in all major enterobacterial species pathogenic to humans or plants (Table 1). The infectious diseases caused by the omptin-expressing bacterial species differ in severity, invasiveness, as well as pathogenetic mechanisms; with the spectrum of clinical associations ranging from the highly fatal plague to beneficial commensalism by faecal Escherichia coli. Recent analyses of omptin functions have indicated that they

Omptin functions are dependent on LPS

LPS is an immunodominant molecule of Gram-negative cell walls and also affects the assembly and folding of several outer membrane proteins, including omptins. Kramer et al. (2000b), Kramer et al. (2002) found that denaturated OmpT can be refolded in the presence of detergents to the β-barrel conformation but the refolding into an active form requires addition of LPS. A similar finding was reported for Pla of Y. pestis (Kukkonen et al., 2004). Biochemical analysis indicated that addition of LPS

The omptins are differently associated with enterobacterial virulence

The available evidence on the possible virulence roles of the omptins does not relieve a single, comprehensive view of their pathogenetic significance, and it rather seems that the individual omptins have evolved to contribute to the life style of their host organisms. The clearest demonstration for a role in virulence is that for Pla of Y. pestis. Presence of the plasmid pPCP1 as well as the expression of Pla activity are associated with the invasive character of plague (Beesley et al., 1967;

The omptins are multifunctional and differ in protease substrates as well as in adhesive and invasive functions

Various molecular functions have been proposed for the omptins. It is striking that, despite of the high overall homology in the protein structures, the individual omptins contribute to very different pathogenetic processes. This results from at least two main reasons: sequence variations at the protein regions important for substrate recognition and the influence of other surface structures, such as LPS, on omptin function.

Functionally, the best-known omptin is Pla of Y. pestis. The prominent

Evolutionary aspects

Comparison of the gene and protein sequences (Table 1; Fig. 2) indicates the presence of two subgroups in the omptin family. The first one is comprised of Pla, PlaA, and PgtE, the other contains OmpT, OmpP, and SopA. In functional properties, Pla and PgtE are closer to each other than to OmpT (Kukkonen et al. (2001), Kukkonen et al. (2004)), and it has been proposed that Pla has originated from PgtE and has been horizontally transferred from the chromosome of S. enterica to Y. pestis (Sodeinde

Acknowledgements

We have been supported by the Academy of Finland (The Microbes and Man Research Programme) and the University of Helsinki.

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ReviewThe omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis

Abstract

Section snippets

Introduction: the omptin family

Omptin functions are dependent on LPS

The omptins are differently associated with enterobacterial virulence

The omptins are multifunctional and differ in protease substrates as well as in adhesive and invasive functions

Evolutionary aspects

Acknowledgements

Int. J. Med. Microbiol.

Methods

Microbes Infect.

FEBS Lett.

FEBS Lett.

FEBS Lett.

FEMS Microbiol. Rev.

FEMS Microbiol. Lett.

FEBS Lett.

Fibrinol. Proteol.

Curr. Opin. Struct. Biol.

Vaccine

J. Biol. Chem.

Gene

Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis

Proc. Natl. Acad. Sci. USA

Pesticins. III. Expression of coagulase and mechanism of fibrinolysis

J. Bacteriol.

Pasteurella pestisrole of pesticin I and iron in experimental plague

Science

Invasion of epithelial cells by Yersinia pestisevidence for a Y. pestis-specific invasin

Infect. Immun.

Substrate specificity of the integral membrane protease OmpT determined by spatially addressed peptide libraries

Biochemistry

SopA, the outer membrane protease responsible for polar localization of IcsA in Shigella flexneri

Mol. Microbiol.

Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica

Mol. Microbiol.

Plasmids in Yersinia pestis

Infect. Immun.

Siderophore-mediated iron transportcrystal structure of FhuA with bound lipopolysaccharide

Science

A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins

Struct. Fold Des.

Bacterial virulence characteristics of E. coli isolates from first-time urinary tract infection

J. Infect. Dis.

Complete nucleotide sequence and deduced amino acid sequence of the ompT gene of E. coli K-12

Nucleic Acids Res.

Review
The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis