The Adhesin Complex Protein (ACP) of Neisseria meningitidis Is a New Adhesin with Vaccine Potential

Hung, Miao-Chiu; Heckels, John E.; Christodoulides, Myron

doi:10.1128/mbio.00041-13

Cited by 45 publications

(73 citation statements)

References 30 publications

(47 reference statements)

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“…4C). In particular, the reduction of cellular adhesion of the NMB2095 is in good agreement with its description as an adhesin (38). The NMB1969 (NalP) mutant did not show a significant change in the level of cell adhesion.…”

Section: Resultssupporting

confidence: 68%

“…A function was assigned to most of the regulated OM proteins, while many of the regulated periplasmic proteins are of as-yet-unknown function. The three most strongly upregulated proteins were the neisserial heparin binding antigen (NHBA, NMB2132) (36), the conserved hypothetical protein NMB1030 (37), and the adhesin complex protein ACP (NMB2095) (38). A role in meningococcal biofilm formation has been described for the NHBA outer membrane protein (39), and ACP is known to facilitate N. meningitidis adherence to different human cell types (38).…”

Section: Resultsmentioning

confidence: 99%

“…The three most strongly upregulated proteins were the neisserial heparin binding antigen (NHBA, NMB2132) (36), the conserved hypothetical protein NMB1030 (37), and the adhesin complex protein ACP (NMB2095) (38). A role in meningococcal biofilm formation has been described for the NHBA outer membrane protein (39), and ACP is known to facilitate N. meningitidis adherence to different human cell types (38). NMB1030 was recently described as a periplasmic ubiquinone-8 binding protein, and yet its function(s) in oxidative stress responses or electron chain transport was not apparent (40).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, NMB2132 (NHBA) is a lipoprotein of the outer membrane and is known to contribute to biofilm formation (39). NMB2095 (ACP) is described as outer membrane adhesin (38) and was thus categorized as an outer membrane protein in our analysis. Outer membrane proteins in Gram-negative bacteria either are lipoproteins or form beta-barrels (58,59).…”

Section: Discussionmentioning

confidence: 99%

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Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome

et al. 2016

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bNeisseria meningitidis, the meningococcus, bears the potential to cause life-threatening invasive diseases, but it usually colonizes the nasopharynx without causing any symptoms. Within the nasopharynx, Neisseria meningitidis must face temperature changes depending on the ambient air temperature. Indeed, the nasopharyngeal temperature can be substantially lower than 37°C, the temperature commonly used in experimental settings. Here, we compared the levels of meningococcal biofilm formation, autoaggregation, and cellular adherence at 32°C and 37°C and found a clear increase in all these phenotypes at 32°C suggestive of a stronger in vivo colonization capability at this temperature. A comparative proteome analysis approach revealed differential protein expression levels between 32°C and 37°C, predominantly affecting the bacterial envelope. A total of 375 proteins were detected. Use of database annotation or the PSORTb algorithm predicted 49 of those proteins to be localized in the outer membrane, 21 in either the inner or outer membrane, 35 in the periplasm, 56 in the inner membrane, and 208 in the cytosol; for 6 proteins, no annotation or prediction was available. Temperature-dependent regulation of protein expression was seen particularly in the periplasm as well as in the outer and inner membranes. Neisserial heparin binding antigen (NHBA), NMB1030, and adhesin complex protein (ACP) showed the strongest upregulation at 32°C and were partially responsible for the observed temperature-dependent phenotypes. Screening of different global regulators of Neisseria meningitidis suggested that the extracytoplasmic sigma factor E might be involved in temperature-dependent biofilm formation. In conclusion, subtle temperature changes trigger adaptation events promoting mucosal colonization by meningococci. Microorganisms constantly adapt to changing environmental conditions. These changes include oxygen and nutrient availability, osmotic conditions, and temperature. The physiology of bacterial adaptation, including the underlying regulatory mechanisms that operate in response to radical temperature changes such as classical heat shock or cold shock, has been studied intensely (1-3). The heat shock response occurs during a transient upshift of growth temperature from 37°C to approximately 50°C (4). The heat shock response is controlled by the alternative sigma factor 32 , which regulates the expression of heat shock proteins mainly involved in protein folding or processing (4). In Escherichia coli, the cold shock response is triggered by a transient downshift from 37°C to 10°C that leads to generally slower transcriptional and translational responses except for about 26 upregulated proteins (5). The functions of these so-called cold shock proteins are less well understood than those of heat shock proteins, but they are likely involved in securing proper transcription, translation, and protein folding (5). Surprisingly little is known about the influence on bacterial physiology of slight temperature differences within mamma...

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Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome

et al. 2016

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“…Human Chang conjunctiva epithelial cells (European Tissue Culture Collection, United Kingdom) were grown in Dulbecco's modified Eagle's medium (DMEM) containing 10% (vol/vol) decomplemented fetal calf sera and a cell lysate prepared by sonication (MSE Soniprep 150 sonicator) as described previously (38). The reactivity of pooled murine antisera to rMIP proteins and of sham-immunized sera, as well as of rabbit anti-rMIP antiserum, was examined initially by Western blot analysis of denatured human cell lysate containing FKBP2, using polyclonal rabbit anti-human FKBP2 (GenBank accession no.…”

Section: Methodsmentioning

confidence: 99%

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

et al. 2015

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A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N-or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (؊LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not ⌬mip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. N eisseria meningitidis (meningococcus) infections contribute significantly to mortality and morbidity worldwide (1). Implementation of capsular polysaccharide-protein conjugate vaccines against serogroups A, C, Y, and W into the routine immunization schedules of developed countries has been successful (2-5), but this approach cannot be used for serogroup B strains. The polysaccharide capsule of serogroup B meningococci (MenB) shows structural mimicry of human fetal brain neural cell adhesion molecules (6). Licensed MenB vaccines based on lipooligosaccharide (LOS)-depleted outer membrane (OM) vesicles (V) have been used to control serosubtype strain-specific clonal outbreaks of MenB infection, e.g., in Norway (7), Cuba (8), Brazil (9), and New Zealand (10), but they do not provide cross-strain protection (11). Recently, the 4CMenB (Bexsero) vaccine, developed using a genome-based reverse-vaccinology approach (12), has received a license from the European Union and has been recommended by the Joint Committee for Vaccination and Immunization for the routine vaccination of infants in the United Kingdom since 2014. The vaccine consists of the factor H binding protein (fHbp, fused to GNA2091 carrier protein), neisserial heparin binding protein (NHBA, fused to GNA1030 carrier protein), and an adhesin, NadA, mixed with the Men...

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Interactions of meningococcal virulence factors with endothelial cells at the human blood–cerebrospinal fluid barrier and their role in pathogenicity

Simonis

Schubert‐Unkmeir

2016

FEBS Letters

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Edited by Wilhelm JustThe Gram-negative extracellular bacterium Neisseria meningitidis is one of the most common aetiological agents of bacterial meningitis affecting predominantly young children worldwide. This bacterium is normally a quiescent coloniser of the upper respiratory tract, but in some individuals it enters the blood stream and causes invasive diseases, such as septicaemia and meningitis. Interactions of N. meningitidis with human endothelial cells are crucially involved in pathogencitiy, and great efforts have been made to understand these molecular interactions. The aim of this review article is to provide an overview of the interactions of meningococcal virulence factors with host endothelial cells at the blood-cerebrospinal fluid barrier.

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The Adhesin Complex Protein (ACP) of Neisseria meningitidis Is a New Adhesin with Vaccine Potential

Cited by 45 publications

References 30 publications

Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome

Impact of Moderate Temperature Changes on Neisseria meningitidis Adhesion Phenotypes and Proteome

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

Interactions of meningococcal virulence factors with endothelial cells at the human blood–cerebrospinal fluid barrier and their role in pathogenicity

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