Bordetella parapertussis Survives the Innate Interaction with Human Neutrophils by Impairing Bactericidal Trafficking inside the Cell through a Lipid Raft-Dependent Mechanism Mediated by the Lipopolysaccharide O Antigen

Gorgojo, Juan Pablo; Lamberti, Yanina Andrea; Valdez, Hugo A.; Harvill, Eric T.; Rodrı́guez, Marı́a Eugenia

doi:10.1128/iai.00662-12

Cited by 18 publications

(39 citation statements)

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“…Recent studies support the hypothesis that B. pertussis is indeed a facultative intracellular bacterium (19). Early studies have suggested that B. parapertussis might also hide inside host cells (11,39), eventually establishing asymptomatic infections. Clinical data have also challenged the assumption that B. parapertussis is strictly extracellular.…”

Section: Discussionmentioning

confidence: 73%

“…In vitro studies confirmed that pertussis acellular vaccines induce antibodies that opsonize B. pertussis but not B. parapertussis (9,10). In the absence of opsonic antibodies, B. parapertussis survives neutrophil phagocytosis by preventing lysosomal maturation in a lipid raft-dependent manner (11). O antigen is involved in this nonbactericidal interaction, mediating the targeting of host cell lipid rafts.…”

mentioning

confidence: 59%

“…Previous studies have shown that B. parapertussis survives innate interaction with human PMN (11). Here, we investigated the outcome of B. parapertussis encounters with macrophages either in the presence or the absence of opsonic antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have demonstrated that B. parapertussis O antigen interaction with cholesterol-rich domains of PMN is critical to avoid the lysosomal pathway and bacterial killing (11). Since B. parapertussis O antigen was involved in the nonbactericidal traf- ficking inside macrophages, we next investigated the role of cholesterol-rich domains in the innate interaction of B. parapertussis with these immune cells.…”

Section: Resultsmentioning

confidence: 99%

“…1C), suggesting that the intracellular fate of B. parapertussis depends on the macrophage receptor(s) targeted during the initial bacteriumhost cell interaction. The O antigen was previously implicated in the survival of B. parapertussis upon interaction with human PMN (11). In order to determine the relevance of O antigen to B. parapertussis survival in its innate interaction with macrophages, we evaluated the outcome of macrophage interaction with an O antigen-deficient mutant of B. parapertussis.…”

Section: Resultsmentioning

confidence: 99%

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Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes

2014

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bBordetella parapertussis is a human pathogen that causes whooping cough. The increasing incidence of B. parapertussis has been attributed to the lack of cross protection induced by pertussis vaccines. It was previously shown that B. parapertussis is able to avoid bacterial killing by polymorphonuclear leukocytes (PMN) if specific opsonic antibodies are not present at the site of interaction. Here, we evaluated the outcome of B. parapertussis innate interaction with human macrophages, a less aggressive type of cell and a known reservoir of many persistent pathogens. The results showed that in the absence of opsonins, O antigen allows B. parapertussis to inhibit phagolysosomal fusion and to remain alive inside macrophages. The O antigen targets B. parapertussis to lipid rafts that are retained in the membrane of phagosomes that do not undergo lysosomal maturation. Fortyeight hours after infection, wild-type B. parapertussis bacteria but not the O antigen-deficient mutants were found colocalizing with lipid rafts and alive in nonacidic compartments. Taken together, our data suggest that in the absence of opsonic antibodies, B. parapertussis survives inside macrophages by preventing phagolysosomal maturation in a lipid raft-and O antigen-dependent manner. Two days after infection, about 15% of macrophages were found loaded with live bacteria inside flotillin-enriched phagosomes that had access to nutrients provided by the host cell recycling pathway, suggesting the development of an intracellular infection. IgG opsonization drastically changed this interaction, inducing efficient bacterial killing. These results highlight the need for B. parapertussis opsonic antibodies to induce bacterial clearance and prevent the eventual establishment of cellular reservoirs of this pathogen. Bordetella parapertussis and Bordetella pertussis are human pathogens that cause whooping cough, a reemerging disease that remains a threat to human health. Despite high vaccination coverage, whooping cough is still endemic. Current clinical surveys indicate that B. parapertussis is responsible for a significant number of cases of whooping cough, particularly in vaccinated populations (1-5). The switch from whole-cell to acellular vaccines is associated with a significant increase in the prevalence of B. parapertussis in the epidemiology of the disease (6, 7). Several studies have demonstrated that pertussis acellular vaccines fail to protect against B. parapertussis (6, 8). The lack of cross protection was mainly attributed to the presence of the O antigen on the surface of B. parapertussis, which blocks antibody access to the vaccine antigens common to both species (9, 10). In vitro studies confirmed that pertussis acellular vaccines induce antibodies that opsonize B. pertussis but not B. parapertussis (9, 10). In the absence of opsonic antibodies, B. parapertussis survives neutrophil phagocytosis by preventing lysosomal maturation in a lipid raft-dependent manner (11). O antigen is involved in this nonbactericidal interaction, mediating t...

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Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes

2014

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Shotgun proteome analysis of Bordetella pertussis reveals a distinct influence of iron availability on the bacterial metabolism, virulence, and defense response

et al. 2015

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One of the mechanisms involved in host immunity is the limitation of iron accessibility to pathogens, which in turn provokes the corresponding physiological adaptation of pathogens. This study reports a gel-free nanoLC-MS/MS-based comparative proteome analysis of Bordetella pertussis grown under iron-excess and iron-depleted conditions. Out of the 926 proteins covered 98 displayed a shift in their abundance in response to low iron availability. Forty-seven of them were found to be increased in level while 58 were found with decreased protein levels under iron starvation. In addition to proteins previously reported to be influenced by iron in B. pertussis, we observed changes in metabolic proteins involved in fatty acid utilization and poly-hydroxybutyrate production. Additionally, many bacterial virulence factors regulated by the BvgAS two-component system were found at decreased levels in response to iron limitation. These results, together with the increased production of proteins potentially involved in oxidative stress resistance, seem to indicate that iron starvation provokes changes in B. pertussis phenotype that might shape host-pathogen interaction.

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Shotgun proteomic analysis of Bordetella parapertussis provides insights into the physiological response to iron starvation and potential new virulence determinants absent in Bordetella pertussis

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Surmann

Gorgojo

et al. 2019

Journal of Proteomics

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Bordetella parapertussis Survives the Innate Interaction with Human Neutrophils by Impairing Bactericidal Trafficking inside the Cell through a Lipid Raft-Dependent Mechanism Mediated by the Lipopolysaccharide O Antigen

Cited by 18 publications

References 39 publications

Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes

Bordetella parapertussis Survives inside Human Macrophages in Lipid Raft-Enriched Phagosomes

Shotgun proteome analysis of Bordetella pertussis reveals a distinct influence of iron availability on the bacterial metabolism, virulence, and defense response

Shotgun proteomic analysis of Bordetella parapertussis provides insights into the physiological response to iron starvation and potential new virulence determinants absent in Bordetella pertussis

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