Monica Konar

• Children's Hospital Oakland Research Institute

Patients receiving eculizumab have an increased risk for meningococcal disease, but most reported cases are attributable to encapsulated meningococcal strains. We describe a case in which a nongroupable meningococcal strain, which rarely causes disease in healthy persons, caused fatal disease in an eculizumab recipient despite meningococcal vaccina...

Key Points Eculizumab, an anti–complement C5 mAb, blocked killing of meningococci by whole blood from healthy immunized adults. Blocking the AP with ACH-4471, a small molecule in development for PNH, had much less of an effect on meningococcal killing.

Background. Complement pathways are important targets for treatment of paroxysmal nocturnalhemoglobinuria (PNH) and autoimmune diseases. Because complement is essential in host defense against Neisseria, patients treated with complement inhibitors are at increased risk of life-threatening meningococcal disease. Meningococcal vaccination is recommen...

Neisseria meningitidis causes cases of bacterial meningitis and sepsis. Factor H binding protein (FHbp) is a component of two licensed meningococcal serogroup B vaccines. FHbp recruits the complement regulator Factor H (FH) to the bacterial surface, which inhibits the complement alternative pathway and promotes immune evasion. Binding of human FH i...

Significance Factor H binding protein (FHbp) is a component of two vaccines recently licensed for prevention of sepsis and meningitis caused by meningococci. FHbp is antigenically variable, and certain sequence variants have low thermal stability. Two amino acid substitutions stabilized a less stable FHbp variant by 21 °C, and the high-resolution c...

Background: Two meningococcal serogroup B vaccines contain Factor H binding protein (FHbp). Binding of Factor H (FH) to FHbp was thought to be specific for human or chimpanzee FH. However, in a previous study an amino acid polymorphism in rhesus macaque FH domain 6, tyrosine at position 352 (Y352) was associated with high binding to FHbp, whereas...

Factor H binding protein (FHbp) is a virulence factor used by meningococci to evade the host complement system. FHbp elicits bactericidal antibodies in humans and is part of two recently licensed vaccines. Using human complement Factor H (FH) transgenic mice, we previously showed that binding of FH decreased the protective antibody responses to FHb...

Background: The meningococcal vaccine antigen, factor H (FH)-binding protein (FHbp), binds human complement FH. In human FH transgenic mice, binding decreased protective antibody responses. Methods: To investigate the effect of primate FH binding, we immunized rhesus macaques with a 4-component serogroup B vaccine (4CMenB). Serum FH in 6 animals...

Annual research function, PGI Chandigarh.

Background: Factor H (fH) binding protein (fHbp) is part of vaccines developed for prevention of meningococcal serogroup B disease. More than 610 fHbp amino acid sequence variants have been identified, which can be classified into 2 subfamilies. The extent of cross-protection within a subfamily has been difficult to assess because of strain variat...

whiB-like genes have been found in all actinomycetes sequenced so far. The amino-acid sequences of WhiB proteins of Mycobacterium tuberculosis H37Rv are highly conserved and participate in several cellular functions. Unlike other WhiB proteins of M. tuberculosis that have properties of protein disulfide reductases, WhiB2 showed properties like a ch...

Enteroaggregative Escherichia coli (EAEC) adherence to human intestinal tissue is known to be mediated by aggregative adherence fimbriae (AAF). However, the host cell molecules involved in EAEC adherence remain uncharacterized. In the present study, four key membrane glycoproteins of cultured human intestinal epithelial cells (INT-407) were found t...

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen, associated with cases of acute and persistent diarrhoea worldwide. The pathogenesis of EAEC is yet to be understood. In intestinal epithelium, an increase in [Ca²⁺](i) has been attributed due to the action of different enteric pathogens. EAEC was shown to increase [Ca²⁺](i)...

Enteroaggregative Escherichia coli (EAEC) is one of the most common bacterial pathogens associated with the etiology of persistent diarrhea. A characteristic feature of EAEC-pathogenesis is the induction of profound inflammatory response in the intestinal epithelium. The present study was designed to investigate the underlying mechanism of inflamma...

Enteroaggregative Escherichia coli (EAEC) is emerging as a cause of acute and persistent diarrhea in developing countries. An important feature of EAEC pathogenesis is the induction of profound inflammatory response in the intestinal epithelium. In this article, we have shown that EAEC-induced activation of mitogen-activated protein kinases (MAPK)...