Intracellular<i>Shigella</i>remodels its LPS to dampen the innate immune recognition and evade inflammasome activation

Paciello, Ida; Silipo, Alba; Fazio, Luigi Lembo; Curcurù, Laura; Zumsteg, Anna Brotcke; Noël, Gaëlle; Ciancarella, Valeria; Sturiale, Luisa; Molinaro, Antonio; Bernardini, Maria Lina

doi:10.1073/pnas.1303641110

Cited by 92 publications

(94 citation statements)

References 72 publications

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“…Other Gram-negative bacterial pathogens with this ability include species of the genera Escherichia (9), Salmonella (10), Yersinia (11), Vibrio (12), and Pseudomonas (13). The capacity of bacteria to adapt to disparate environments is likely imparted by numerous evolved strategies that probably include modification of outer membrane macromolecules (14)(15)(16)(17). Outer membrane fluidity and permeability are partly modulated by hydrophobic acyl chains of lipid A regions of lipopolysaccharide (LPS) (18).…”

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confidence: 99%

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

et al. 2015

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Leptospirosis is an emerging disease with an annual occurrence of over 1 million human cases worldwide. Pathogenic Leptospira bacteria are maintained in zoonotic cycles involving a diverse array of mammals, with the capacity to survive outside the host in aquatic environments. Survival in the diverse environments encountered by Leptospira likely requires various adaptive mechanisms. Little is known about Leptospira outer membrane modification systems, which may contribute to the capacity of these bacteria to successfully inhabit and colonize diverse environments and animal hosts. Leptospira bacteria carry two genes annotated as UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase genes (la0512 and la4326 [lpxD1 and lpxD2]) that in other bacteria are involved in the early steps of biosynthesis of lipid A, the membrane lipid anchor of lipopolysaccharide. Inactivation of only one of these genes, la0512/lpxD1, imparted sensitivity to the host physiological temperature (37°C) and rendered the bacteria avirulent in an animal infection model. Polymyxin B sensitivity assays revealed compromised outer membrane integrity in the lpxD1 mutant at host physiological temperature, but structural analysis of lipid A in the mutant revealed only minor changes in the lipid A moiety compared to that found in the wild-type strain. In accordance with this, an in trans complementation restored the phenotypes to a level comparable to that of the wild-type strain. These results suggest that the gene annotated as lpxD1 in Leptospira interrogans plays an important role in temperature adaptation and virulence in the animal infection model. Members of the genus Leptospira are spirochete bacteria encompassing saprophytic and pathogenic species and are considered to be the most widespread zoonotic bacteria worldwide (1). Leptospira is the etiological agent of the disease leptospirosis, which in severe manifestations leads to hemorrhage in the lungs, meningitis, and liver and/or kidney failure (1). Leptospirosis is an emerging disease, and the worldwide annual occurrence is estimated to be over 1 million human cases, with a 5 to 20% mortality rate (2, 3). Leptospira cannot breach the host epidermal lining, and transmission requires direct contact of the bacteria with cuts or abrasions in the skin (4, 5). Rats and other rodent species serve as reservoir hosts for Leptospira, which colonizes the urinary systems of these animals (6). Leptospira is shed back into the environment through the urine of reservoir hosts and can persist in freshwater and soil until direct contact with an animal recommences an infection cycle (7,8).A prominent Leptospira feature is the ability to proliferate under significantly different environmental conditions. Other Gram-negative bacterial pathogens with this ability include species of the genera Escherichia (9), Salmonella (10), Yersinia (11), Vibrio (12), and Pseudomonas (13). The capacity of bacteria to adapt to disparate environments is likely imparted by numerous evolved strategies that probably include modi...

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Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

et al. 2015

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“…Lipopolysaccharide (LPS) is a potent bacterial effector triggering the activation of the innate immune system following binding with the complex CD14, myeloid differentiation protein 2, and Toll-like receptor 4 (Paciello et al, 2013).…”

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Evidence-guided optimization of herbal formula Cheong-Hwa-Bo-Um-Tang using multiplex cytokine profiling

Lee¹,

Park²

2016

Afr. J. Trad. Compl. Alt. Med.

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Background: Cheong-Hwa-Bo-Um-Tang (CHB) has been traditionally used to treat pharyngolaryngitis and throat inflammation in Korea. However, the anti-inflammatory activity of CHB and the exact component proportion ratio of CHB have not been fully reported. Materials and Methods: This study was conducted to optimize the component proportion ratio of CHB on the basis of experimental evidence using multiplex cytokine profiling assay in LPS-stimulated RAW 264.7 mouse macrophages. Results: The optimized CHB (named Chunhwabun-Cheong-Hwa-Bo-Um-Tang) inhibited the production of NO, IL-6, MCP-1, GM-CSF, IL-10, IP-10, VEGF, M-CSF, RANTES, MIP-1β, LIF, LIX, and TNF-α in LPS-stimulated RAW 264.7 mouse macrophages without decreasing cell viability (P<0.05). Chunhwabun-Cheong-Hwa-Bo-Um-Tang consisted of roots of Scrophularia buergeriana, Trichosanthes kirilowii, Anemarrhena asphodeloides, Phellodendron amurense, Angelica gigas, Rehmannia glutinosa, Paeonia japonica, Cnidium officinale, and Glycyrrhiza uralensis (in the ratio of 8: 3: 3: 3: 3: 4: 4: 3: 3). Conclusion:The results of this study indicate that the multiplex cytokine profiling assay could be one of the effective methods for evidence-guided optimization of the component proportion ratio of a traditional herbal formula used for treating excessive inflammation such as the cytokine storm.

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“…For example, Paciello et al observe that upon entry into epithelial cells, intracellular Shigella remodels its lipopolysaccharide (LPS) to evade recognition by the host innate immune system. 13 Similarly, using shotgun proteomics to globally characterize the protein content of Shigella grown in broth versus within the epithelial cell cytosol, 14 Pieper et al observe marked differences, both increases and decreases, in the levels of multiple outer membrane proteins. While these studies did not observe significant increases in levels of detectable ProV or ProW and only a 2-fold increase in ProX, they did observe a significant increase in the level of OsmC, a protein whose expression is induced by hyperosmolarity.…”

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confidence: 99%

How to manage stress: Lessons from an intracellular pathogen

Janakiraman

Lesser

2016

Virulence

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IntracellularShigellaremodels its LPS to dampen the innate immune recognition and evade inflammasome activation

Abstract: 110(46):E4345-5

Cited by 92 publications

References 72 publications

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

Evidence-guided optimization of herbal formula Cheong-Hwa-Bo-Um-Tang using multiplex cytokine profiling

How to manage stress: Lessons from an intracellular pathogen

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