Zinc is a bivalent cation essential for bacterial growth and metabolism. The human pathogenNeisseria meningitidisexpresses a homologue of the Zinc uptake regulator Zur, which has been postulated to repress the putative zinc uptake protein ZnuD. In this study, we elucidated the transcriptome of meningococci in response to zinc by microarrays and quantitative real-time PCR (qRT-PCR). We identified 15 genes that were repressed and two genes that were activated upon zinc addition. All transcription units (genes and operons) harbored a putative Zur binding motif in their promoter regions. A meningococcal Zur binding consensus motif (Zur box) was deducedin silico, which harbors a conserved central palindrome consisting of hexameric inverted repeats separated by three nucleotides (TGTTATDNHATAACA).In vitrobinding of recombinant meningococcal Zur to this Zur box was shown for the first time using electrophoretic mobility shift assays. Zur binding to DNA depended specifically on the presence of zinc and was sensitive to mutations in the palindromic sequence. The Zur regulon among genes of unknown function comprised genes involved in zinc uptake, tRNA modification, and ribosomal assembly. In summary, this is the first study of the transcriptional response to zinc in meningococci.

Intentional burns represent a serious form of physical abuse that must be identified to protect children from further harm. This study is a retrospectively planned secondary analysis of the Examining Siblings To Recognize Abuse (ExSTRA) network data. Our objective was to describe the characteristics of burns injuries in children referred to Child Abuse Pediatricians (CAPs) in relation to the perceived likelihood of abuse. We furthermore compare the extent of diagnostic investigations undertaken in children referred to CAPs for burn injuries with those referred for other reasons. Within this dataset, 7% (215/2890) of children had burns. Children with burns were older than children with other injuries (median age 20 months vs. 10 months). Physical abuse was perceived as likely in 40.9% (88) and unlikely in 59.1% (127). Scalds accounted for 52.6% (113) and contact burns for 27.6% (60). Several characteristics of the history and burn injury were associated with a significantly higher perceived likelihood of abuse, including children with reported inflicted injury, absent or inadequate explanation, hot water as agent, immersion scald, a bilateral/symmetric burn pattern, total body surface area ≥10%, full thickness burns, and co-existent injuries. The rates of diagnostic testing were significantly lower in children with burns than other injuries, yet the yield of skeletal survey and hepatic transaminases testing were comparable between the two groups. This would imply that children referred to CAPs for burns warrant the same level of comprehensive investigations as those referred for other reasons.

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Neisseria meningitidis employs polysaccharides and outer membrane proteins to cope with human serum complement attack. To screen for factors influencing serum resistance, an assay was developed based on a colorimetric serum bactericidal assay. The screening used a genetically modified sequence type (ST)-41/44 clonal complex (cc) strain lacking LPS sialylation, polysaccharide capsule, the factor H binding protein (fHbp) and MutS, a protein of the DNA repair mechanism. After killing of >99.9% of the bacterial cells by serum treatment, the colorimetric assay was used to screen 1000 colonies, of which 35 showed enhanced serum resistance. Three mutant classes were identified. In the first class of mutants, enhanced expression of Opc was identified. Opc expression was associated with vitronectin binding and reduced membrane attack complex deposition confirming recent observations. Lipopolysaccharide (LPS) immunotype switch from immunotype L3 to L8/L1 by lgtA and lgtC phase variation represented the second class. Isogenic mutant analysis demonstrated that in ST-41/44 cc strains the L8/L1 immunotype was more serum resistant than the L3 immunotype. Consecutive analysis revealed that the immunotypes L8 and L1 were frequently observed in ST-41/44 cc isolates from both carriage and disease. Immunotype switch to L8/L1 is therefore suggested to contribute to the adaptive capacity of this meningococcal lineage. The third mutant class displayed a pilE allelic exchange associated with enhanced autoaggregation. The mutation of the C terminal hypervariable region D of PilE included a residue previously associated with increased pilus bundle formation. We suggest that autoaggregation reduced the surface area accessible to serum complement and protected from killing. The study highlights the ability of meningococci to adapt to environmental stress by phase variation and intrachromosomal recombination affecting subcapsular antigens.

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