Haemophilus influenzaelocalized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity

Schilfgaarde, Muriel van; Eijk, Paul P.; Regelink, Annette G.; Ulsen, Peter van; Everts, V.; Dankert, J.; Alphen, Loek van

doi:10.1006/mpat.1998.0269

Cited by 56 publications

(65 citation statements)

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“…In~36 % of our subjects, NTHi strains persisted in the NP or middle ear after antibiotic treatment, a finding similar to that of van Schilfgaarde et al (1999) and others (Cohen et al, 1999;Dabernat et al, 1998). Strains that persist in the NP after antibiotic therapy may be the result of antibiotic resistance or other unique characteristics of the strain or could be a consequence of lower levels of antibiotic in a host due to suboptimal absorption of the drug (Pichichero et al, 2008;Pichichero & Reed, 2009).…”

Section: Discussionsupporting

confidence: 91%

“…Inc means it was not possible to obtain a sequence for all seven genes for that isolate and therefore the ST was not obtained, but partial analysis clearly allowed us to determine that the strain was different from the other strains in that particular child. MLST types in invasive disease, so we cannot determine whether ST146 and ST685 are associated or not with invasive disease.In~36 % of our subjects, NTHi strains persisted in the NP or middle ear after antibiotic treatment, a finding similar to that of van Schilfgaarde et al (1999) and others (Cohen et al, 1999;Dabernat et al, 1998). Strains that persist in the NP after antibiotic therapy may be the result of antibiotic resistance or other unique characteristics of the strain or could be a consequence of lower levels of antibiotic in a host due to suboptimal absorption of the drug (Pichichero et al, 2008;Pichichero & Reed, 2009).…”

supporting

confidence: 91%

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Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Kaur

Chang

et al. 2011

Journal of Medical Microbiology

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The phylogenetic relationships of non-typable Haemophilus influenzae (NTHi) strains prospectively isolated from healthy children and children with acute otitis media (AOM) were analysed using multilocus sequence typing (MLST). A total of 165 NTHi isolates were collected over a 3.5 year time frame during 2006 through 2009. The strains were tested for b-lactamase production; 28.5 % were positive. Seventy different NTHi sequence types (STs) were identified of which 29 (41.4 %) were novel. NTHi strains did not show any phylogenetic grouping or clustering among asymptomatic colonizing strains or strains that caused AOM, or based on b-lactamase enzyme production. Evaluation of triplets and other siblings over time demonstrated relatively frequent genetic exchanges in NTHi isolates in vivo in a short time frame and subsequent transfer among children in a family. Comparison of the MLST STs isolated at different time points showed that in~85 % of the nasopharynx (NP) colonizations, NTHi strains cleared from the host within 3 months, that sequential colonization in the same child involved different strains in all cases except one, and that NP and middle ear isolates were identical STs in 84 % of cases. In this first study of its type to our knowledge, we could not identify predominant MLST types among strains colonizing the NP versus those causing AOM or expressing a b-lactamase enzyme conferring penicillin resistance in children. INTRODUCTIONNon-typable Haemophilus influenzae (NTHi) is an important human-specific pathogen colonizing the nasopharynx (NP) of the upper respiratory tract (Faden et al., 1995; Murphy et al., 2009). NTHi strains are rarely associated with invasive disease in children, but they are associated with respiratory tract infections in both children and adults (Murphy, 2003;Kyd & Cripps, 1999). NP colonization with NTHi is an important risk factor for developing disease (Faden et al., 1997). Children frequently NP-colonized by NTHi are more likely to develop acute otitis media (AOM) than less frequently colonized children (Faden et al., 1997; Harabuchi et al., 1994). Simultaneous detection of multiple isolates of NTHi from the same sample has been reported among aboriginal children with otitis media (Smith-Vaughan et al., 1996), among otitis-prone children in day care centres (St Sauver et al., 2000) and in cystic fibrosis patients (Bandi et al., 2001; Murphy et al., 1999), which may result from inadequate clearance of colonizing bacteria, exposure to multiple circulating strains or in vivo genetic recombinations in a specific host. It is not known whether NTHi isolates that express b-lactamases (responsible for resistance to b-lactam antibiotics such as penicillins, cephamycins and carbapenems) are phylogenetically related. Various studies of Streptococcus pneumoniae have shown phylogenetic relationships among antibiotic-resistant strains (Beall et al., 2006;Hanage et al., 2009;Porat et al., 2004;Xu et al., 2009). In this study, we explored whether or not NTHi shows genetic relatedness in relation...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 91%

Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Kaur

Chang

et al. 2011

Journal of Medical Microbiology

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“…Data from other groups support the idea of bacteria using the paracellular route to cross epithelial barriers. For H. influenzae, van Schilfgaarde et al (24) showed that passage through a polarized epithelial barrier occurs between cells by paracytosis. It was also suggested that the ability of H. influenzae to penetrate the epithelial layer protects them from antibiotics and antibody-mediated bactericidal activity (25).…”

Section: Discussionmentioning

confidence: 99%

“…For H. influenzae, van Schilfgaarde et al (24) showed that passage through a polarized epithelial barrier occurs between cells by paracytosis. It was also suggested that the ability of H. influenzae to penetrate the epithelial layer protects them from antibiotics and antibody-mediated bactericidal activity (25). Burkholderia cenocepacia also disrupts a differentiated epithelial barrier, an event associated with loss of occludin from tight junctions (26).…”

Section: Discussionmentioning

confidence: 99%

Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Beißwenger

Coyne

Shchepetov

et al. 2007

Journal of Biological Chemistry

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Streptococcus pneumoniae and Haemophilus influenzae are human pathogens that often asymptomatically colonize the mucosal surface of the upper respiratory tract, but also occasionally cause invasive disease. The ability of these species to traverse the epithelium of the airway mucosa was modeled in vitro using polarized respiratory epithelial cells in culture. Migration across the epithelial barrier was preceded by loss of transepithelial resistance. Membrane products of S. pneumoniae that included lipoteichoic acid induced disruption of the epithelial barrier in a Toll-like receptor 2-dependent manner. This result correlates with a recent genetic study that associates increased TLR2 signaling with increased rates of invasive pneumococcal disease in humans. Loss of transepithelial resistance by the TLR2 ligand correlated with activation of p38 MAP kinase and transforming growth factor (TGF)-␤ signaling. Activation of p38 MAPK and TGF-␤ signaling in epithelial cells upon nasal infection with S. pneumoniae was also demonstrated in vivo. Inhibition of either p38 MAPK or TGF-␤ signaling was sufficient to inhibit the migration of S. pneumoniae or H. influenzae. Our data shows that diverse bacteria utilize common mechanisms, including MAPK and TGF-␤ signaling pathways to disrupt epithelial barriers and promote invasion.

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“…Persistence of certain bacteria in the lower respiratory tract of COPD patients may be due to localisation to protected sites. H. influenzae is localised to sites within the airway wall, such as between cells in the airway walls [261] and these organisms are not susceptible to antibiotics or antibody-mediated defence mechanisms when they are located between airway epithelial cells [262]. H. influenzae infection is associated with increased concentrations of inflammatory mediators, including IL-8 and TNF-a, in COPD patients [263].…”

Section: What Are the Mechanisms Of Acute Exacerbations?mentioning

confidence: 99%

Chronic obstructive pulmonary disease: molecular and cellularmechanisms

Barnes

Shapiro²,

Pauwels³

2003

Eur Respir J

1,216

966

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Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease. Eur Respir J 2003; 22: 672-688.

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Haemophilus influenzaelocalized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity

Cited by 56 publications

References 0 publications

Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media

Role of p38 MAP Kinase and Transforming Growth Factor-β Signaling in Transepithelial Migration of Invasive Bacterial Pathogens

Chronic obstructive pulmonary disease: molecular and cellularmechanisms

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