<i>Streptococcus pneumoniae</i>Forms Surface‐Attached Communities in the Middle Ear of Experimentally Infected Chinchillas

Reid, Sean D.; Hong, Wenzhou; Dew, Kristin E.; Winn, Dana; Pang, Bing; Watt, James; Glover, David T.; Hollingshead, Susan K.; Swords, W. Edward

doi:10.1086/597042

Cited by 100 publications

(101 citation statements)

References 49 publications

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“…This would suggest that increased pneumococcal-epithelial cell adherence is unlikely to be relevant to bacterial OM. Previous studies in the chinchilla suggest that pneumococci persist in the middle ear by forming biofilms consisting of bacterial components and host components derived from the influx of neutrophils (30). Given that in the present study (i) neutrophils were the predominant cellular infiltrate in the middle ear and (ii) pneumococci colocalized with the neutrophils in the middle ear, a similar mechanism of disease may be occurring in our murine model.…”

Section: Discussionsupporting

confidence: 71%

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

et al. 2013

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dInfluenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.

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Section: Discussionsupporting

confidence: 71%

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

et al. 2013

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“…This hypothesis has been supported by both animal model studies in experimentally infected chinchillas (20,36,58) and a prospective clinical trial in which bacterial biofilms of H. influenzae, S. pneumoniae, and M. catarrhalis were directly detected on the MEM epithelia obtained from children undergoing TT placement for the treatment of COM (28). No evidence of OM pathogens was found on the MEM of uninfected animals or in humans in a control population without a history of OM undergoing surgery for the placement of cochlear implants, suggesting that pathogenic biofilms are not present on the MEM in the absence of middle-ear disease.…”

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confidence: 70%

Adenoid Reservoir for Pathogenic Biofilm Bacteria

et al. 2011

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Biofilms of pathogenic bacteria are present on the middle ear mucosa of children with chronic otitis media (COM) and may contribute to the persistence of pathogens and the recalcitrance of COM to antibiotic treatment. Controlled studies indicate that adenoidectomy is effective in the treatment of COM, suggesting that the adenoids may act as a reservoir for COM pathogens. To investigate the bacterial community in the adenoid, samples were obtained from 35 children undergoing adenoidectomy for chronic OM or obstructive sleep apnea. We used a novel, culture-independent molecular diagnostic methodology, followed by confocal microscopy, to investigate the in situ distribution and organization of pathogens in the adenoids to determine whether pathogenic bacteria exhibited criteria characteristic of biofilms. The Ibis T5000 Universal Biosensor System was used to interrogate the extent of the microbial diversity within adenoid biopsy specimens. Using a suite of 16 broad-range bacterial primers, we demonstrated that adenoids from both diagnostic groups were colonized with polymicrobial biofilms. Haemophilus influenzae was present in more adenoids from the COM group (P ‫؍‬ 0.005), but there was no significant difference between the two patient groups for Streptococcus pneumoniae or Staphylococcus aureus. Fluorescence in situ hybridization, lectin binding, and the use of antibodies specific for host epithelial cells demonstrated that pathogens were aggregated, surrounded by a carbohydrate matrix, and localized on and within the epithelial cell surface, which is consistent with criteria for bacterial biofilms.

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“…Based on recent work from our group, it is now clear that biofilms formed during experimental otitis media include a significant host component (22,43). Biofilms recovered from experimental otitis media infections contain a double-stranded DNA lattice (27) to which bactericidal factors such as histone and elastase are attached (22).…”

Section: Discussionmentioning

confidence: 99%

Nontypeable Haemophilus influenzae Initiates Formation of Neutrophil Extracellular Traps

et al. 2011

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Nontypeable Haemophilus influenzae (NTHI) is a leading cause of otitis media infections, which are often chronic and/or recurrent in nature. NTHI and other bacterial species persist in vivo within 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 formation in vitro. In this study, the ability of NTHI and NTHI components to initiate NET formation was examined using an in vitro model 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.Nontypeable Haemophilus influenzae (NTHI) is a common commensal of the human nasopharynx, in which setting carriage is usually asymptomatic and without adverse effect. When host mucociliary clearance is impaired, NTHI can cause localized opportunistic infections within the airway (14). For example, NTHI is a leading cause of otitis media (OM), which is among the most common and costly pediatric infections and can be a persistent and/or recurrent infection (30). Persistent populations of NTHI in vivo during chronic and recurrent otitis media are found within biofilm communities within the middle-ear chamber (19,40). Other factors that provide an environment for NTHI to cause infections include age, genetic predisposition, atopy, and immune system impairment (44), as well as Eustachian tube dysfunction and pressure dysregulation caused by virus-induced congestion (11,12,33). Biofilms have long been thought to promote microbial resistance to pharmaceutical or immune clearance during persistent infections (17,20). Bacterial factors important to NTHI biofilms include specific subsets of lipooligosaccharides (LOS) containing sialic acid and/or phosphorylcholine (23, 24, 45), pili (28), and double-stranded DNA (25,27). Our recent work demonstrated that NTHI biofilms also have a significant host component, including a double-stranded DNA lattice decorated with histones and elastase, that fits the defining traits of a neutrophil extracellular trap (NET) (22)....

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Streptococcus pneumoniaeForms Surface‐Attached Communities in the Middle Ear of Experimentally Infected Chinchillas

Cited by 100 publications

References 49 publications

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

Adenoid Reservoir for Pathogenic Biofilm Bacteria

Nontypeable Haemophilus influenzae Initiates Formation of Neutrophil Extracellular Traps

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