Innate immune evasion mediated by picornaviral 3C protease: Possible lessons for coronaviral 3C‐like protease?

ABSTRACT We hypothesize a potential role for Borrelia burgdorferi OspC in innate immune evasion at the initial stage of mammalian infection. We demonstrate that B. burgdorferi is resistant to high levels (>200 μg/ml) of cathelicidin and that this antimicrobial peptide exhibits limited binding to the spirochetal outer membrane, irrespective of OspC or other abundant surface lipoproteins. We conclude that the essential role of OspC is unrelated to resistance to this component of innate immunity.

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Plasticity in early immune evasion strategies of a bacterial pathogen

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1718595115 ◽

2018 ◽

Vol 115 (16) ◽

pp. E3788-E3797 ◽

Cited By ~ 6

Author(s):

Quentin Bernard ◽

Alexis A. Smith ◽

Xiuli Yang ◽

Juraj Koci ◽

Shelby D. Foor ◽

...

Keyword(s):

Immune Evasion ◽

Bacterial Pathogen ◽

Surface Protein ◽

Innate Immune ◽

Serum Complement ◽

Term Survival ◽

Evasion Strategy ◽

Innate Immune Evasion ◽

Novel Therapeutic

Borrelia burgdorferiis one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy ofB. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.

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Intracellular survival and innate immune evasion of Burkholderia cepacia : Improved understanding of quorum sensing‐controlled virulence factors, biofilm, and inhibitors

Microbiology and Immunology ◽

10.1111/1348-0421.12762 ◽

2020 ◽

Vol 64 (2) ◽

pp. 87-98 ◽

Cited By ~ 3

Author(s):

Pitchaipillai Sankar Ganesh ◽

Sivakumar Vishnupriya ◽

Jamuna Vadivelu ◽

Vanitha Mariappan ◽

Kumutha M. Vellasamy ◽

...

Keyword(s):

Quorum Sensing ◽

Virulence Factors ◽

Immune Evasion ◽

Burkholderia Cepacia ◽

Intracellular Survival ◽

Innate Immune ◽

Innate Immune Evasion

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Early evolutionary loss of the lipid A modifying enzyme PagP resulting in innate immune evasion in Yersinia pestis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1917504117 ◽

2020 ◽

Vol 117 (37) ◽

pp. 22984-22991 ◽

Cited By ~ 3

Author(s):

Courtney E. Chandler ◽

Erin M. Harberts ◽

Mark R. Pelletier ◽

Iyarit Thaipisuttikul ◽

Jace W. Jones ◽

...

Keyword(s):

Yersinia Pestis ◽

Immune Evasion ◽

Lipid A ◽

Yersinia Pseudotuberculosis ◽

Innate Immune ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Structural Modifications ◽

Tlr4 Signaling Pathway ◽

Innate Immune Evasion

Immune evasion through membrane remodeling is a hallmark of Yersinia pestis pathogenesis. Yersinia remodels its membrane during its life cycle as it alternates between mammalian hosts (37 °C) and ambient (21 °C to 26 °C) temperatures of the arthropod transmission vector or external environment. This shift in growth temperature induces changes in number and length of acyl groups on the lipid A portion of lipopolysaccharide (LPS) for the enteric pathogens Yersinia pseudotuberculosis (Ypt) and Yersinia enterocolitica (Ye), as well as the causative agent of plague, Yersinia pestis (Yp). Addition of a C16 fatty acid (palmitate) to lipid A by the outer membrane acyltransferase enzyme PagP occurs in immunostimulatory Ypt and Ye strains, but not in immune-evasive Yp. Analysis of Yp pagP gene sequences identified a single-nucleotide polymorphism that results in a premature stop in translation, yielding a truncated, nonfunctional enzyme. Upon repair of this polymorphism to the sequence present in Ypt and Ye, lipid A isolated from a Yp pagP+ strain synthesized two structures with the C16 fatty acids located in acyloxyacyl linkage at the 2′ and 3′ positions of the diglucosamine backbone. Structural modifications were confirmed by mass spectrometry and gas chromatography. With the genotypic restoration of PagP enzymatic activity in Yp, a significant increase in lipid A endotoxicity mediated through the MyD88 and TRIF/TRAM arms of the TLR4-signaling pathway was observed. Discovery and repair of an evolutionarily lost lipid A modifying enzyme provides evidence of lipid A as a crucial determinant in Yp infectivity, pathogenesis, and host innate immune evasion.

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