<i>Neisseria gonorrhoeae</i>
            Porin P1.B Induces Endosome Exocytosis and a Redistribution of Lamp1 to the Plasma Membrane

Ayala, Patricia; Vasquez, Brandi; Wetzler, Lee M.; So, Magdalene

doi:10.1128/iai.70.11.5965-5971.2002

Cited by 22 publications

(32 citation statements)

References 40 publications

(50 reference statements)

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“…N. gonorrhoeae Tfp are retractile fibers on the bacterial surface that promote adhesion and host cell signaling (18, 28, 53, 55, 63–66). Tfp retraction is mediated by PilT, the Tfp retraction motor (25).…”

Section: Resultsmentioning

confidence: 99%

Presenilin/γ-Secretase Cleaves CD46 in Response to Neisseria Infection

Weyand

Calton

Higashi

et al. 2009

The Journal of Immunology

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CD46 is a type I transmembrane protein with complement and T cell regulatory functions in human cells. CD46 has signaling and receptor properties in immune and nonimmune cells, many of which are dependent on the expression of cytoplasmic tail (cyt) isoforms cyt1 or cyt2. Little is known about how cyt1 and cyt2 mediate cellular responses. We show that CD46-cyt1 and CD46-cyt2 are substrates for presenilin/γ-secretase (PS/γS), an endogenous protease complex that regulates many important signaling proteins through proteolytic processing. PS/γS processing of CD46 releases immunoprecipitable cyt1 and cyt2 tail peptides into the cell, is blocked by chemical inhibitors, and is prevented in dominant negative presenilin mutant cell lines. Two human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, stimulate PS/γS processing of CD46-cyt1 and CD46-cyt2. This stimulation requires type IV pili and PilT, the type IV pilus retraction motor, implying that mechanotransduction plays a role in this event. We present a model for PS/γS processing of CD46 that provides a mechanism by which signals are transduced via the cyt1 and cyt2 tails to regulate CD46-dependent cellular responses. Our findings have broad implications for understanding the full range of CD46 functions in infection and noninfection situations.

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Section: Resultsmentioning

confidence: 99%

Presenilin/γ-Secretase Cleaves CD46 in Response to Neisseria Infection

Weyand

Calton

Higashi

et al. 2009

The Journal of Immunology

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“…For the experiments described in this work, A431 cells (20), an epithelial cell line derived from the endocervix (56), were used. Gonococci have been shown to adhere to and invade A431 cells at a high frequency (3,30,43,48,76), and there have been several reports investigating the response of these cells to gonococcal adherence at the molecular level (4,5,7,43).…”

Section: Resultsmentioning

confidence: 99%

Global Gene Expression and the Role of Sigma Factors in Neisseria gonorrhoeae in Interactions with Epithelial Cells

Lenz

Arvidson

2005

Infect Immun

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Like many bacterial pathogens, Neisseria gonorrhoeae must adapt to environmental changes in order to successfully colonize and proliferate in a new host. Modulation of gene expression in response to environmental signals is an efficient mechanism used by bacteria to achieve this goal. Using DNA microarrays and a tissue culture model for gonococcal infection, we examined global changes in gene expression in N. gonorrhoeae in response to adherence to host cells. Among those genes induced upon adherence to human epithelial cells in culture was rpoH, which encodes a homolog of the heat shock sigma factor, 32 (RpoH), as well as genes of the RpoH regulon, groEL and groES. Attempts to construct an rpoH null mutant in N. gonorrhoeae were unsuccessful, suggesting that RpoH is essential for viability of N. gonorrhoeae. The extracytoplasmic sigma factor, RpoE ( E ), while known to regulate rpoH in other bacteria, was found not to be necessary for the up-regulation of rpoH in gonococci upon adherence to host cells. To examine the role of RpoH in host cell interactions, an N. gonorrhoeae strain conditionally expressing rpoH was constructed. The results of our experiments showed that while induction of rpoH expression is not necessary for adherence of gonococci to epithelial cells, it is important for the subsequent invasion step, as gonococci depleted for rpoH invade cells two-to threefold less efficiently than a wild-type strain. Taken together, these results indicate that 32 , but not E , is important for the response of gonococci in the initial steps of an infection.

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“…However, because IgA1 protease cleavage of LAMP1 in vitro was less efficient at low pH than at neutral pH, it is hypothesized that cleavage takes place not in lysosomes but at the plasma membrane (43). Indeed, neisserial porin and pilin trigger endosome and lysosome exocytosis, redistributing LAMP1 to the plasma membrane, which is thought to reduce the total number of lysosomes in infected cells (50)(51)(52). Our data show that IgaB-mediated cleavage of LAMP1 is also more efficient at neutral pH, but we observed no redistribution of lysosomes in our infection model system.…”

Section: Discussionmentioning

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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Neisseria gonorrhoeae Porin P1.B Induces Endosome Exocytosis and a Redistribution of Lamp1 to the Plasma Membrane

Cited by 22 publications

References 40 publications

Presenilin/γ-Secretase Cleaves CD46 in Response to Neisseria Infection

Presenilin/γ-Secretase Cleaves CD46 in Response to Neisseria Infection

Global Gene Expression and the Role of Sigma Factors in Neisseria gonorrhoeae in Interactions with Epithelial 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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