Nontypeable Haemophilus influenzae isolated from intractable acute otitis media internalized into cultured human epithelial cells

Hotomi, Muneki; Arai, Jun; Billal, Dewan S.; Takei, Shin; Ikeda, Yorihiko; Ogami, Masashi; Kono, Masamitsu; Beder, Levent Bekir; Toya, Kazuo; Kimura, Michio; Yamanaka, Noboru

doi:10.1016/j.anl.2009.03.012

Cited by 36 publications

(26 citation statements)

References 26 publications

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“…When indicated, cells were pretreated with AZM (with various dose ranges, depending on the NTHI strain and type of assay) or vehicle solution (sterile water) for 30 min; the drug/vehicle was then removed before NTHI infection. AZM doses and regimens were selected according to previous studies (40)(41)(42)53) and according to the susceptibility to AZM of the NTHI strains under study. Alternatively, cells were infected as described above, and AZM (with various dose ranges, depending on the NTHI strain and assay) or vehicle solution (sterile water) was added during the gentamicin incubation period.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the observed increased macrolide resistance by colonizing respiratory pathogens generates doubts about its long-term low-dose prophylactic use. Independent studies with unrelated NTHI isolates displaying different degrees of AZM susceptibility have shown a bactericidal effect of AZM against intracellular NTHI (40)(41)(42), and the therapeutic efficacy of macrolides has been suggested by use of mouse and rat NTHI pulmonary infection models (32,(43)(44)(45)(46). In this study, we questioned the effects of both prophylactic and therapeutic uses of AZM, the relationship between NTHI AZM resistance and administration effects, and the antimicrobial versus immunomodulatory effects of AZM on NTHI respiratory infection.…”

Section: N Ontypeable (Noncapsulated) Haemophilus Influenzae (Nthi)mentioning

confidence: 98%

See 1 more Smart Citation

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Euba

Moleres

Viadas

et al. 2015

Antimicrob Agents Chemother

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Section: Methodsmentioning

confidence: 99%

Section: N Ontypeable (Noncapsulated) Haemophilus Influenzae (Nthi)mentioning

confidence: 98%

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Euba

Moleres

Viadas

et al. 2015

Antimicrob Agents Chemother

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“…After three other washes with cacodylate buffer at 4 8C for 10 min each, samples were postfixed for 15 min at room temperature in 2% osmium tetroxide in deionized water. Specimens were dehydrated in a graded series of ethanol solutions and desiccated in a critical point dryer apparatus (Bal-Tec CPD 030) (Hotomi et al, 2010). After an ion-spatter coating with gold-palladium, samples were viewed with a JSM-6480 JEOL scanning electron microscope .…”

Section: Cell Invasion Assaysmentioning

confidence: 99%

Haemophilus parasuis serovar 5 Nagasaki strain adheres and invades PK-15 cells

Frandoloso

Martínez-Martínez

Gutiérrez-Martín

et al. 2012

Veterinary Microbiology

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“…However, for several decades, studies have reported significant numbers of NTHI within and between a variety of human respiratory epithelial and subepithelial cells and macrophages in vitro and ex vivo, including the bronchi of adults with chronic lung disease and the adenoids of children with adenoidal hypertrophy or with a history of chronic otitis media (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Few studies have examined the internalization, trafficking, and fate of NTHI in host cells.…”

mentioning

confidence: 99%

Internalization and Trafficking of Nontypeable Haemophilus influenzae in Human Respiratory Epithelial Cells and Roles of IgA1 Proteases for Optimal Invasion and Persistence

2014

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Nontypeable Haemophilus influenzae (NTHI) is a leading cause of opportunistic infections of the respiratory tract in children and adults. Although considered an extracellular pathogen, NTHI has been observed repeatedly within and between cells of the human respiratory tract, and these observations have been correlated to symptomatic infection. These findings are intriguing in light of the knowledge that NTHI persists in the respiratory tract despite antibiotic therapy and the development of bactericidal antibodies. We hypothesized that intracellular NTHI avoids, escapes, or neutralizes the endolysosomal pathway and persists within human respiratory epithelial cells and that human IgA1 proteases are required for optimal internalization and persistence of NTHI. Virtually all strains encode a human IgA1 protease gene, igaA, and we previously characterized a novel human IgA1 protease gene, igaB, that is associated with disease-causing strains and is homologous to the IgA1 protease that is unique to pathogenic Neisseria spp. Here, we show that NTHI invades human bronchial epithelial cells in vitro in a lipid raft-independent manner, is subsequently trafficked via the endolysosomal pathway, and is killed in lysosomes after variable durations of persistence. IgaA is required for optimal invasion. IgaB appears to play little or no role in adherence or invasion but is required for optimal intracellular persistence of NTHI. IgaB cleaves lysosome-associated membrane protein 1 (LAMP1) at pHs characteristic of the plasma membrane, early endosome, late endosome, and lysosome. However, neither IgA1 protease inhibits acidification of intracellular vesicles containing NTHI. NTHI IgA1 proteases play important but different roles in NTHI invasion and trafficking in respiratory epithelial cells. Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative, human-exclusive commensal bacterium of the nasopharynx and is a leading cause of opportunistic infections in the upper and lower respiratory tracts, including otitis media, sinusitis, conjunctivitis, community-acquired pneumonia, and exacerbations of chronic obstructive pulmonary disease (COPD) and of cystic fibrosis (1, 2).When a new strain of NTHI is acquired, the outcome depends on a variety of dynamic host and bacterial factors. Colonization and the transition from commensal to opportunistic pathogen require NTHI to resist host innate immune defenses, including nutrient sequestration, mucociliary clearance, antimicrobial peptides, secretory IgA1, and phagocytosis by immune cells or by epithelial cells. Bacterial counterresistance mechanisms under investigation include adhesins, antimicrobial peptide degradation, IgA1 protease, biofilm production, modification of surface-exposed lipooligosaccharide moieties, production of outer membrane vesicles (OMVs), and others (3-12). Understanding these factors will help identify targets for therapeutic intervention, as NTHI infections induce acquired immunity consisting largely of strain-specific bactericidal antibodies that afford littl...

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Nontypeable Haemophilus influenzae isolated from intractable acute otitis media internalized into cultured human epithelial cells

Cited by 36 publications

References 26 publications

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Haemophilus parasuis serovar 5 Nagasaki strain adheres and invades PK-15 cells

Internalization and Trafficking of Nontypeable Haemophilus influenzae in Human Respiratory Epithelial Cells and Roles of IgA1 Proteases for Optimal Invasion and Persistence

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