1,721,503 research outputs found
Application for consent to release a GMO – organisms other than higher plants: Experimental challenge of the human nasopharynx with recombinant Neisseria lactamica expressing the meningococcal type V autotransporter protein, Neisseria Adhesin A (NadA).
No full textThe purpose of the genetic modification is to construct a strain of the exclusively human, nasopharyngeal commensal bacterium, Neisseria lactamica (Nlac) that expresses on its surface the outer membrane protein, Neisseria Adhesin A (NadA). NadA is an adhesin protein found in the close relative of Nlac, Neisseria meningitidis (Nmen), which is the causative agent of meningococcal disease. The genetically modified organism (GMO) will be used to investigate the role of NadA in the colonisation of the nasopharynx and associated immune responses in a controlled human bacterial challenge. The Experimental Human Challenge group, previously based at the University of Sheffield and now located at the University of Southampton, has conducted two previous human bacterial challenges in adult volunteers, using wild type Nlac strain, Y92-1009. The primary objective of the proposed study is to verify that nasopharyngeal challenge of humans with GM-Nlac is safe. Secondary objectives are determining the impact of NadA expression on the frequency of nasopharyngeal colonisation by GM-Nlac and the type(s) of immune responses generated locally and systemically to these bacteria. Ultimately this strategy may confer benefit as a bacterial medicine expressing genes with therapeutic or prophylactic potential within the human nasopharynx
Neisseria meningitidis and meningococcal disease: recent discoveries and innovations
No full textPURPOSE OF REVIEW: Meningococcal disease is a severe consequence of infection with Neisseria meningitidis, a pathobiont of the pharynx. This organism is panmitic so virulent clones transformed with new genetic material can emerge and cause severe outbreaks. The key to sustainable prevention is to restrict carriage of disease-causing strains and thus reduce the chances of transmission between human hosts.RECENT FINDINGS: Meningococcal population biology has changed recently with emergence of virulent strains linked to a number of sublineages of clonal complex 11. These strains have variously expressed the capsular material of serogroups C and W and caused severe disease in various countries. Glycoconjugate vaccines including quadrivalent (ACWY) and now pentavalent (ACWYX) vaccines are highly immunogenic and prevent disease and carriage due to their respective serogroups. For NmB, new vaccines (4CMenB and MenB-FHbp) containing conserved outer membranes proteins have been deployed and are immunogenic and protective at population level, but clones exist which do not express cognate antigens. In contrast to glycoconjugate vaccines they may not have potent carriage-reducing activity. Mass chemoprophylaxis is gaining credence as an alternative strategy is effective, but has significant shortcomings in sustainability.SUMMARY: Meningococcal disease is well defined genomically for epidemiological purposes. There is potential for unpredictable emergence of clones that may have reduced susceptibility even to modern vaccines, and continued surveillance and vigilance is necessary. However, tremendous strides have been made in recent years.</p
Using the NIHR comprehensive clinical research network for infectious diseases and microbiology research
No full textAnti-adhesion methods as novel therapeutics for bacterial infections
No full textAnti-adhesion therapies for bacterial infections offer an alternative to antibiotics, with those therapies bacteria are not killed but are prevented from causing harm to a host by inhibiting adherence to host cells and tissues, a prerequisite for the majority of infectious diseases. The mechanisms of these potential therapeutic agents include inhibition of adhesins and their host receptors, vaccination with adhesins or analogs, use of probiotics and dietary supplements that interfere with receptor-adhesin interactions, subminimal inhibitory concentrations of antibiotics and manipulation of hydrophobic interactions. Once developed, these drugs will contribute to the arsenal for fighting infectious disease in the future, potentially subverting antibiotic resistance
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