Abstract
BackgroundMeningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.MethodsA cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.ResultsOf 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09–0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07–0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.ConclusionsIn adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.
Highlights
Neisseria meningitidis is an obligate commensal of the human nasopharyngeal mucosa and is found in 10–20% of healthy individuals [1,2]
Meningococcal colonization usually is observed as asymptomatic carrier state, but may progress towards invasive bacterial infections varying from transient blood infection, to meningitis and fulminant septic shock with high mortality and morbidity rates [3,4]
We showed that in adults with meningococcal meningitis, infection with lipid A variants is associated with a milder clinical course of disease with reduced coagulopathy and systemic inflammation [15]
Summary
Neisseria meningitidis is an obligate commensal of the human nasopharyngeal mucosa and is found in 10–20% of healthy individuals [1,2]. Incidence of meningococcal disease shows its primary peak in children aged ,5 years of age with up to 20 cases per 100,000 per year in infants under 1 year of age [5]. This increased susceptibility has been attributed to an immature immune system and lack of protective antibodies [6,7]. Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
