The OmpA-Like Protein Loa22 Is Essential for Leptospiral Virulence

Ristow, Paula; Bourhy, Pascale; McBride, Flávia W. da C.; Figueira, Cláudio Pereira; Huerre, Michel; Avé, Patrick; Girons, Isabelle Saint; Ko, Albert I.; Picardeau, Mathieu

doi:10.1371/journal.ppat.0030097

Cited by 218 publications

(228 citation statements)

References 34 publications

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“…The surface localization studies confirmed that the OmpA-like protein of Francisella is localized to the outer membrane, suggesting that surface exposed regions exist. Similar features have been reported for OmpA-like protein of Leptospira interrogans (41). In vivo, the FTL_0325 mutant of F. tularensis LVS was found to be highly attenuated for virulence in mice and induced an early inflammatory response.…”

Section: Discussionsupporting

confidence: 79%

Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response

Mahawar

Atianand

Dotson

et al. 2012

Journal of Biological Chemistry

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Background:The mechanism of immune suppression caused by Francisella tularensis SchuS4 strain, a category A agent, are yet unknown. Results: FTL_0325/FTT0831c genes of F. tularensis suppress proinflammatory cytokines by preventing activation of NF-B signaling. Conclusion: FTL_0325/FTT0831c of Francisella is a key virulence factor and functions as an immunosuppressant. Significance: Understanding of such pathogenic mechanisms will define vaccine candidates to prevent tularemia acquired naturally or through an act of bioterrorism.

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Section: Discussionsupporting

confidence: 79%

Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response

Mahawar

Atianand

Dotson

et al. 2012

Journal of Biological Chemistry

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“…The molecular pathogenesis of leptospirosis is poorly understood, and the bacterial virulence factors involved are largely unknown. Recently, several potential Leptospira virulence factors have been described, including sphingomyelinases, serine proteases, zinc-dependent proteases, and collagenase (3); LipL32 (4); lipopolysaccharide (5); a novel factor H, laminin, and Fn-binding protein (Lsa24 or Len) (6 -8); Loa 22 (9); and Lig (Leptospiral immunoglobulin-like) proteins (10 -12).…”

mentioning

confidence: 99%

Fibronectin Binds to and Induces Conformational Change in a Disordered Region of Leptospiral Immunoglobulin-like Protein B

Lin¹,

Greenwood

Nicholson

et al. 2009

Journal of Biological Chemistry

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Leptospira interrogans is a pathogenic spirochete that causes disease in both humans and animals. LigB (Leptospiral immunoglobulin-like protein B) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin (Fn), fibrinogen, laminin, and collagen. A high affinity Fn-binding region of LigB has been recently localized to LigBCen2, which contains the partial eleventh and full twelfth immunoglobulin-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, LigBCen2NR was shown to bind to the N-terminal domain (NTD) of Fn (K D ‫؍‬ 379 nM) by an enzyme-linked immunosorbent assay and isothermal titration calorimetry. Interestingly, this sequence was not observed to adopt secondary structure by far UV circular dichroism or by differential scanning calorimetry, in agreement with computer-based secondary structure predictions. A low partition coefficient (K av ) measured with gel permeation chromatography, a high hydrodynamic radius (R h ) measured with dynamic light scattering, and the insensitivity of the intrinsic viscosity to guanidine hydrochloride treatment all suggest that LigBCen2NR possesses an extended and disordered structure. Two-dimensional 15 N-1 H HSQC NMR spectra of intact LigBCen2 in the absence and presence of NTD are consistent with these observations, suggesting the presence of both a ␤-rich region and an unstructured region in LigBCen2 and that the latter of these selectively interacts with NTD. Upon binding to NTD, LigBCen2NR was observed by CD to adopt a ␤-strand-rich structure, suggestive of the known ␤-zipper mode of NTD binding.Leptospira interrogans is a pathogenic spirochete that causes leptospirosis throughout the world, especially in developing countries but also in regions of the United States where it has reemerged (1). Weil's syndrome, a severe form of this disease, is an acute febrile illness associated with multiorgan damage, including liver failure (jaundice), renal failure (nephritis), pulmonary hemorrhage, and meningitis (1), and has a 15% mortality rate if not treated (2). The molecular pathogenesis of leptospirosis is poorly understood, and the bacterial virulence factors involved are largely unknown. Recently, several potential Leptospira virulence factors have been described, including sphingomyelinases, serine proteases, zinc-dependent proteases, and collagenase (3); LipL32 (4); lipopolysaccharide (5); a novel factor H, laminin, and Fn-binding protein (Lsa24 or Len) (6 -8); Loa 22 (9); and Lig (Leptospiral immunoglobulin-like) proteins (10 -12).Lig proteins, including LigA, LigB, and LigC, contain multiple immunoglobulin-like repeat domains (13 in LigA, 12 in LigB and LigC) (10 -12). Interestingly, the first 630 residues, from the N terminus to the first half of the seventh immunoglobulinlike domain, are conserved between LigA and LigB, but the rest of the immunoglobulin-like domains are variable (10 -12) between the two proteins. Also, a non-immunoglobulin-like repeat region found on the C-terminal...

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“…This protein functions as both an evasin and target of the mammalian immune system, a modulator of biofilm formation, and as a bacteriophage receptor (11). Additionally, functional studies with several pathogenic bacteria, including Leptospira interrogans (12), Neisseria gonorrhoeae (13), Salmonella enterica (14), and E. coli (15) have demonstrated a direct role for OmpA in virulence phenotypes upon host infection. No information exists on the function of bacterial OmpA as it relates to host-symbiont homeostasis.…”

mentioning

confidence: 99%

An insect symbiosis is influenced by bacterium-specific polymorphisms in outer-membrane protein A

Weiss

Schwank

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Beneficial bacterial symbioses are ubiquitous in nature. However, the functional and molecular basis of host tolerance to resident symbiotic microbes, in contrast to resistance to closely related bacteria that are recognized as foreign, remain largely unknown. We used the tsetse fly (Glossina morsitans), which depends on symbiotic flora for fecundity and has limited exposure to foreign microbes, to investigate the tolerance phenomenon exhibited during symbiosis. We examined the potential role of bacterium-specific polymorphisms present in the major bacterial surface protein, outer-membrane protein A (OmpA), on host infection outcomes. Tsetse were successfully superinfected with their mutualistic facultative symbiont, Sodalis glossinidius, whereas infections with Escherichia coli K12 were lethal. In contrast, tsetse were resistant to an E. coli OmpA mutant strain, whereas recombinant Sodalis expressing E. coli OmpA became pathogenic. Profiling of tsetse immunity-related gene expression incriminated peptidoglycan recognition protein (pgrp)-lb as a determinant of the infection outcomes we observed. RNAi-induced knockdown of tsetse pgrp-lb significantly reduced host mortality after infection with otherwise lethal E. coli K12. Our results show that polymorphisms in the exposed loop domains of OmpA represent a microbial adaptation that mediates host tolerance of endogenous symbiotic bacteria.peptidoglycan recognition protein LB ͉ Sodalis glossinidius ͉ tsetse

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The OmpA-Like Protein Loa22 Is Essential for Leptospiral Virulence

Cited by 218 publications

References 34 publications

Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response

Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response

Fibronectin Binds to and Induces Conformational Change in a Disordered Region of Leptospiral Immunoglobulin-like Protein B

An insect symbiosis is influenced by bacterium-specific polymorphisms in outer-membrane protein A

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