scholarly journals Survival of Bacterial Biofilms within Neutrophil Extracellular Traps Promotes Nontypeable Haemophilus influenzae Persistence in the Chinchilla Model for Otitis Media

2009 ◽  
Vol 1 (3) ◽  
pp. 215-224 ◽  
Author(s):  
Wenzhou Hong ◽  
Richard A. Juneau ◽  
Bing Pang ◽  
W. Edward Swords
Keyword(s):  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Neutrophil Extracellular Traps ◽  
Bacterial Biofilms ◽  
Extracellular Traps

scholarly journals Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps

2014 ◽  
Vol 83 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Richard A. Juneau ◽  
Bing Pang ◽  
Chelsie E. Armbruster ◽  
Kyle A. Murrah ◽  
Antonia C. Perez ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Stress Responses ◽  
Neutrophil Extracellular Traps ◽  
Infection Model ◽  
Chronic Obstructive ◽  
Bacterial Persistence ◽  
Extracellular Traps ◽  
Airway Infections

NontypeableHaemophilus influenzae(NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded byhktE) and a bifunctional peroxiredoxin-glutaredoxin (encoded bypdgX) in resistance of NTHI to oxidants and persistencein vivo. Isogenic NTHI strain 86-028NP mutants lackinghktEandpdgXhad increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed thatpdgXandhktEwere important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilmsin vivo. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs.

scholarly journals NontypeableHaemophilus influenzaeInitiates Formation of Neutrophil Extracellular Traps

2010 ◽  
Vol 79 (1) ◽  
pp. 431-438 ◽  
Author(s):  
Richard A. Juneau ◽  
Bing Pang ◽  
Kristin E. D. Weimer ◽  
Chelsie E. Armbruster ◽  
W. Edward Swords
Keyword(s):  
Otitis Media ◽  
Bacterial Species ◽  
Outer Membrane Proteins ◽  
Neutrophil Extracellular Traps ◽  
Bacterial Surface ◽  
Persistent Infections ◽  
Extracellular Traps ◽  
Molecular Patterns

ABSTRACTNontypeableHaemophilus influenzae(NTHI) is a leading cause of otitis media infections, which are often chronic and/or recurrent in nature. NTHI and other bacterial species persistin vivowithin biofilms during otitis media and other persistent infections. These biofilms have a significant host component that includes neutrophil extracellular traps (NETs). These NETs do not mediate clearance of NTHI, which survives within NET structures by means of specific subpopulations of lipooligosaccharides on the bacterial surface that are determinants of biofilm formationin vitro. In this study, the ability of NTHI and NTHI components to initiate NET formation was examined using anin vitromodel system. Both viable and nonviable NTHI strains were shown to promote NET formation, as did preparations of bacterial DNA, outer membrane proteins, and lipooligosaccharide (endotoxin). However, only endotoxin from a parental strain of NTHI exhibited equivalent potency in NET formation to that of NTHI. Additional studies showed that NTHI entrapped within NET structures is resistant to both extracellular killing within NETs and phagocytic killing by incoming neutrophils, due to oligosaccharide moieties within the lipooligosaccharides. Thus, we concluded that NTHI elicits NET formation by means of multiple pathogen-associated molecular patterns (most notably endotoxin) and is highly resistant to killing within NET structures. These data support the conclusion that, for NTHI, formation of NET structures may be a persistence determinant by providing a niche within the middle-ear chamber.

scholarly journals Nontypeable Haemophilus influenzae redox recycling of protein thiols promotes resistance to oxidative killing and bacterial survival in biofilms in a smoke related infection model

2021 ◽  
Author(s):  
Benjamin C. Hunt ◽  
Xin Xu ◽  
Amit Gaggar ◽  
W. Edward Swords
Keyword(s):  
Oxidative Stress ◽  
Haemophilus Influenzae ◽  
Bacterial Load ◽  
Redox Homeostasis ◽  
Neutrophil Extracellular Traps ◽  
Immunofluorescent Staining ◽  
Extracellular Traps ◽  
Protein Thiols ◽  
Mutant Strains ◽  
Thiol Peroxidase

AbstractSmoke exposure is a risk factor for community acquired pneumonia, which is typically caused by host adapted opportunists like nontypeable Haemophilus influenzae (NTHi). Genomic analyses of NTHi revealed homologs of enzymes involved in thiol metabolism, which can have key roles in oxidant resistance. Using a clinical NTHi isolate (NTHi 7P49H1), we generated isogenic mutant bacterial strains in which homologs of glutathione reductase (NTHI 0251), thiol peroxidase (NTHI 0361), thiol peroxidase (NTHI 0907), thioredoxin reductase (NTHI 1327) and glutaredoxin/peroxiredoxin (NTHI 0705) were inactivated. Bacterial protein analyses revealed significant increases in protein oxidation after oxidative stress for all the mutant strains. Similarly, each of these mutants were less resistant to oxidative killing compared with the parental strain; these phenotypes were reversed by genetic complementation. Quantitative confocal analysis of biofilms showed reducted biofilm thickness and density, and significant sensitization of bacteria within the biofilm structure to oxidative killing for thiol mutant strains. Smoke-exposed mice infected with NTHi 7P49H1 showed significantly increased lung bacterial load, as compared to control mice. Immunofluorescent staining of lung tissues showed NTHi communities on the lung mucosa, interspersed with host neutrophil extracellular traps; these bacteria had surface moieties associated with the Hi biofilm matrix, and transcript profiles consistent with NTHi biofilms. In contrast, infection with the panel of NTHi mutants showed significant decrease in lung bacterial load. Comparable results were observed in bactericidal assays with neutrophil extracellular traps in vitro. Thus, we conclude that thiol mediated redox homeostasis promotes persistence of NTHi within biofilm communities.ImportanceChronic bacterial respiratory infections are a significant problem for smoke exposed individuals, especially those with chronic obstructive pulmonary disease (COPD). These infections often persist despite antibiotic use. Thus, the bacteria remain and contribute to the development of inflammation and other respiratory problems. Respiratory bacteria often form biofilms within the lungs, while growing in a biofilm their antibiotic and oxidative stress resistance is incredibly heightened. It is well documented that redox homeostasis genes are upregulated during this phase of growth. Many common respiratory pathogens such as NTHi and Streptococcus pneumoniae are reliant on scavenging from the host the necessary components they need to maintain these redox systems. This work here begins to lay down the foundation for exploiting this requirement and thiol redox homeostasis pathways of these bacteria as a therapeutic target for managing chronic respiratory bacterial infections, which are resistant to traditional antibiotic treatments alone.

scholarly journals Stuck in the glue – Biofilms, intracellular bacteria and neutrophil extracellular traps in otitis media

2016 ◽  
Vol 130 (S3) ◽  
pp. S34-S34
Author(s):  
Ruth Thornton ◽  
Stephanie Jeffares ◽  
Shyan Vijayasekaran ◽  
Lea-Ann Kirkham ◽  
Selma Wiertsema ◽  
...  
Keyword(s):  
Otitis Media ◽  
Neutrophil Extracellular Traps ◽  
Intracellular Bacteria ◽  
Extracellular Traps

scholarly journals Neutrophil Extracellular Traps and Fibrin in Otitis Media

2017 ◽  
Vol 143 (10) ◽  
pp. 990 ◽  
Author(s):  
Patricia A. Schachern ◽  
Geeyoun Kwon ◽  
David E. Briles ◽  
Patricia Ferrieri ◽  
Steven Juhn ◽  
...  
Keyword(s):  
Otitis Media ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps
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