<i>Haemophilus influenzae</i>Forms Biofilms on Airway Epithelia

Starner, Timothy D.; Zhang, Niu; Kim, GunHee; Apicella, Michael A.; McCray, Paul B.

doi:10.1164/rccm.200509-1459oc

Cited by 188 publications

(159 citation statements)

References 47 publications

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“…More detailed analysis by scanning electron microscopy showed dense multilayered bacterial communities (Fig. 5C) that are reminiscent of those observed by our group and others in vitro (12,38,43,48).…”

Section: Resultssupporting

confidence: 82%

Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media

et al. 2007

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Haemophilus influenzae is a gram-negative pleiomorphic bacterium that is a common commensal/mutualist within the human airways (30). Encapsulated H. influenzae strains are overt pathogens causing invasive disease (3) and have largely been contained by a vaccine effective against the predominant capsular serotype b strains (32). In contrast, the so-called nontypeable H. influenzae (NTHi) strains lacking capsular polysaccharides remain predominant in asymptomatic carriage and localized airway infections (14, 29). These infections are mostly opportunistic in nature and include bronchiopneumonia, sinusitis, and otitis media (OM). OM is among the most common pediatric infections, causing an estimated ϳ$5 billion in costs of treatment and parents' missed work days per year (20). OM infections include chronic OM that is difficult to resolve with antibiotic therapy, and it has long been postulated that chronic OM involves the formation of bacterial biofilm communities (5, 35). In support of that hypothesis, biofilms have been visualized in tympanostomy drain tubes removed from patients with OM and on middle ear tissue from experimentally infected chinchillas (7,18,33). More recent evidence shows that NTHi and other bacterial agents are present within biofilms on tissue specimens obtained from patients with chronic and recurrent OM (13).The H. influenzae surface is covered with lipooligosaccharide (LOS) endotoxins that lack a repeating O side chain. Instead, the H. influenzae LOS features a diverse collection of LOS glycoforms that differ in the length, content, and nature of the chemical linkages found in the oligosaccharide portion. These LOS oligosaccharides include structures that are antigenically similar to host cell-surface glycolipids and may also contain the host membrane constituents sialic acid (NeuAc) and phosphorylcholine (PCho) (41). LOS confers resistance to host killing (8,9,37) and is also the primary target of the Toll-like receptor 4 pathway that mediates protection against H. influenzae in the airways (47). It has been established that NTHi strains that express NeuAc-LOS forms comprise a greater proportion of biofilm communities than of planktonic cultures, and that mutations eliminating these forms decrease biofilm formation and bacterial persistence in animal models of OM (4,12,18,43). More recently, we showed that LOS purified from biofilms has decreased potency as an inflammatory agonist, which correlated with an increase in PCho ϩ LOS forms that were present within biofilms (55). In this study, we compared the virulence

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Section: Resultssupporting

confidence: 82%

Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media

et al. 2007

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“…Images were acquired at 2.0 μ m intervals down through the biofi lm Z-stack (μ m). Therefore, the number of images in each stack varied according to the biomass and average thickness of the biofi lm (Starner et al 2006). Quantifi cation of biofi lm biomass and average thickness was calculated using a MatLab 5.3 (The MathWork, Inc., Natick, MA, USA), equipped with an Image Processing Toolbox and COMSTAT analysis.…”

Section: Quantifi Cation Of Biofi Lm Structuresmentioning

confidence: 99%

“…For quantifi cation of biofi lm mass, each datapoint used was the mean biomass of four randomly imaged areas from a single biofi lm. Mean biomass values from different biofi lm experiments were used for further statistical analyses (Starner et al 2006).…”

Section: Statistical Tests and Data Analysismentioning

confidence: 99%

Antimicrobial Effect of Fluoroquinolones for the Eradication of Nontypeable Haemophilus Influenzae Isolates within Biofilms

Kaji

Watanabe

Apicella

et al. 2008

Tohoku J. Exp. Med.

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Biofi lms can be defi ned as communities of microorganisms attached to a surface. Those bacterial biofi lms cause serious problems, such as antibiotic resistance and medical devicerelated infections. Nontypeable Haemophilus infl uenzae (NTHi) is an important pathogen in respiratory infections, as it forms biofi lms both in vitro and in vivo such as human middle ear. Recent reports indicate that otitis media, paranasal sinusitis and lower respiratory tract infections caused by Haemophilus infl uenzae have become more diffi cult to treat with oral antibiotic therapy. However, there has been no attention given to antibiotic eradication of NTHi biofi lm. To investigate the antimicrobial effect of various antibiotics against NTHi biofi lm formation, we conducted the following comparative study using both β -lactamase-negative ampicillin (AMP)-susceptible (BLNAS) and AMP-resistant (BLNAR) NTHi strains. In a microtiter biofi lm assay, both levofl oxacin and gatifl oxacin, of the fl uoroquinolone antibiotic group, signifi cantly inhibited biofi lm formation by BLNAS and BLNAR NTHi in a dose-dependent fashion compared to ampicillin of the penicillin antibiotic group, cefotaxime of the cephalosporin antibiotic group, and both erythromycin and clarithromycin of the macrolide antibiotic group. Furthermore, in fl ow cell chamber studies, confocal laser scanning microscopy counted survival bacteria in mature biofi lm had been treated with gatifl oxacin, ampicillin, cefotaxime and erythromycin. Only gatifl oxacin completely killed the BLNAR NTHi isolates within biofi lms without regard to the thickness of biofi lm formation. The results of this study suggest that fl uoroquinolones potentially have a role in therapy against diseases caused by both BLNAS and BLNAR NTHi isolates within biofi lms.

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“…Bacterial species isolated from cases with respiratory tract infections usually show strong resistance to antimicrobial agents; this could be related to the potential for biofi lm formation in respiratory tract. According to Starner et al 6 , bacterial biofi lms are increasingly recognized as the cause of persistence and disease pathogenesis in respiratory infections, such as CF 6 .…”

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confidence: 99%

Synergistic interactions in mixed-species biofilms of pathogenic bacteria from the respiratory tract

Varposhti

Entezari

Feizabadi

2014

Rev. Soc. Bras. Med. Trop.

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Introduction: Mixed-species biofi lms are involved in a wide variety of infections. We studied the synergistic interactions during dual-species biofi lm formation among isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: Isolates were cultured as single-species and all possible combinations of dual-species biofi lms. Results: The 61 A. baumannii biofi lms increased by 26-fold when cultured with S. maltophilia isolates; 62 A. baumannii biofi lms increased by 20-fold when cultured with S. maltophilia isolates; and 31 P. aeruginosa biofi lms increased by 102-fold when cultured with S. maltophilia 106. Conclusions: Synergy was observed between two isolates, including those that inherently lacked biofi lm formation ability.

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Haemophilus influenzaeForms Biofilms on Airway Epithelia

Cited by 188 publications

References 47 publications

Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media

Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media

Antimicrobial Effect of Fluoroquinolones for the Eradication of Nontypeable Haemophilus Influenzae Isolates within Biofilms

Synergistic interactions in mixed-species biofilms of pathogenic bacteria from the respiratory tract

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