Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

Shah, Nita R.; Hancock, Robert E. W.; Fernandez, Rachel C.

doi:10.1128/aac.02590-14

Cited by 39 publications

(30 citation statements)

References 13 publications

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“…The naturally occurring B. pertussis strains described here could also be less virulent due to similar mechanisms. These strains do not activate TLR4 signaling and, in addition, the lack of GlcN modification of the LOS molecules leads to decreased resistance to antimicrobial peptides, as shown in recent studies using GLcN Ϫ mutants of B. pertussis and the closely related B. bronchiseptica (67,68). This however remains to be investigated in larger clinical cohorts.…”

Section: Discussionmentioning

confidence: 90%

Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

et al. 2015

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bBordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to different B. pertussis clinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate that B. pertussis isolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.T he innate immune system is the first line of defense against invading pathogens. In order to recognize these microorganisms, innate immune cells express multiple pathogen recognition receptors (PRR) consisting of various receptor families, including the most-studied Toll-like receptors (TLRs) (1). Evasion of this first recognition can be critical for the pathogen establishing infection. Additionally, the innate immune system is essential for the induction and regulation of the adaptive response. For example, dendritic cells (DCs) can produce interleukin-12p70 (IL12p70), which is associated with the differentiation of T helper 1 (Th1) cells or cytotoxic T cells (2, 3) and IL-1␤, IL-6, and IL-23, which are required for differentiation and survival of Th17 cells (4, 5). Pathogen adaptation, through changes in the structure or expression of molecules which interact with the host, might allow the pathogen to escape the host immune responses.Pertussis, also referred to as whooping cough, is a humanspecific respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. It has been shown that B. pertussis is able to activate both TLR2 and TLR4 signaling on innate immune cells, which is essential for inducing protective immunity against this bacterium (6-9). A well-defined ligand for TLR4 is lipopolysaccharide (LPS), which is produced by Gram-nega...

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Section: Discussionmentioning

confidence: 90%

Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

et al. 2015

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“…Prevention of electrostatic binding of AMPs to the Gram-negative cell surface is achieved by amine-containing molecules (amino sugars, phosphoethanolamine (PEA) or glycine), which increase the positive charge of the anionic LPS component lipid A. P. aeruginosa and S. typhimurium attach aminoarabinose to a phosphate group in lipid A [96,97]. Acinetobacter baumannii, Francisella novicida and Bordetella species modify lipid A phosphate with galactosamine or glucosamine [98][99][100][101]. Furthermore, Gram-negative bacteria use PEA to decrease the anionic properties of LPS.…”

Section: Surface Modificationmentioning

confidence: 99%

Bacterial strategies of resistance to antimicrobial peptides

Joo

Otto

2016

Phil. Trans. R. Soc. B

279

238

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One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Antimicrobial peptides (AMPs) are a key component of the host's innate immune system, targeting invasive and colonizing bacteria. For successful survival and colonization of the host, bacteria have a series of mechanisms to interfere with AMP activity, and AMP resistance is intimately connected with the virulence potential of bacterial pathogens. In particular, because AMPs are considered as potential novel antimicrobial drugs, it is vital to understand bacterial AMP resistance mechanisms. This review gives a comparative overview of Gram-positive and Gram-negative bacterial strategies of resistance to various AMPs, such as repulsion or sequestration by bacterial surface structures, alteration of membrane charge or fluidity, degradation and removal by efflux pumps.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

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“…This modification was found to confer resistance to AMPs, and reduce outer membrane perturbation by EDTA [112].…”

Section: Accepted Manuscriptmentioning

confidence: 94%

Defensive remodeling: How bacterial surface properties and biofilm formation promote resistance to antimicrobial peptides

Nuri

Shprung

Shai

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Multidrug resistance bacteria are a major concern worldwide. These pathogens cannot be treated with conventional antibiotics and thus alternative therapeutic agents are needed. Antimicrobial peptides (AMPs) are considered to be good candidates for this purpose. Most AMPs are short and positively charged amphipathic peptides, which are found in all known forms of life. AMPs are known to kill bacteria by binding to the negatively charged bacterial surface, and in most cases cause membrane disruption. Resistance toward AMPs can be developed, by modification of bacterial surface molecules, secretion of protective material and up-regulation or elimination of specific proteins. Because of the general mechanisms of attachment and action of AMPs, bacterial resistance to AMPs often involves biophysical and biochemical changes such as surface rigidity, cell wall thickness, surface charge, as well as membrane and cell wall modification. Here we focus on the biophysical, surface and surrounding changes that bacteria undergo in acquiring resistance to AMPs. In addition we discuss the question of whether bacterial resistance to administered AMPs might compromise our innate immunity to endogenous AMPs. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.

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Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

Cited by 39 publications

References 13 publications

Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

Bacterial strategies of resistance to antimicrobial peptides

Defensive remodeling: How bacterial surface properties and biofilm formation promote resistance to antimicrobial peptides

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