The Neisseria meningitidis Serogroup A Capsular Polysaccharide O-3 and O-4 Acetyltransferase

Gudlavalleti, Seshu K.; Datta, Anup; Tzeng, Yih-Ling; Noble, Corie; Carlson, Russell W.; Stephens, David S.

doi:10.1074/jbc.m313552200

Cited by 48 publications

(53 citation statements)

References 59 publications

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“…Two separate peaks, one of the O-acetylated form at lower-field signal (5.40 ppm) and the other of the non-O-acetylated form at upper-field signal (5.35 ppm) were resolved (Figure 2). Isolate 1666, with a stop codon in the csaC gene encoding an O-acetyltransferase with specificity for the O-3 and O-4 positions in ManNAc [17], expressed normal amounts of capsular material (Table 1), but no O-acetylation was detected (Figure 2). Neither the monoclonal nor the polyclonal capsular polysaccharide antiserum was able to bind to this non-O-acetylated polysaccharide (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…O-acetylation is an important final step modification of the A polysaccharide polymer, and a dramatic reduction in immunogenicity is associated with the removal of the O-acetyl groups [19,44]. Many pathogenic bacteria are O-acetylated, but CsaC has no homology to other known O-acetyltransferases or to the sialic acid serogroup C, Y, and W capsule O -acetyltransferases (OatC and OatWY) [17]. In our study, we found that the carriage isolate 1666 had a stop mutation in the csaC gene coding for the meningococcal serogroup A O-3 and O-4 ManNAc acetyltransferase [17].…”

Section: Discussionmentioning

confidence: 99%

“…Many pathogenic bacteria are O-acetylated, but CsaC has no homology to other known O-acetyltransferases or to the sialic acid serogroup C, Y, and W capsule O -acetyltransferases (OatC and OatWY) [17]. In our study, we found that the carriage isolate 1666 had a stop mutation in the csaC gene coding for the meningococcal serogroup A O-3 and O-4 ManNAc acetyltransferase [17]. Neither the anti-A capsule mAb nor the polyclonal anti-capsular antiserum elicited by the ACWY conjugate vaccine Menveo recognized the non-O-acetylated polysaccharide resulting in a complete lack of bactericidal activity of the anti-ACWY capsule antiserum.…”

Section: Discussionmentioning

confidence: 99%

“…The serogroup A polysaccharide consists of repeating units of (α1-6)-linked N- acetyl-mannosamine-1-phosphate synthesized by enzymes encoded by genes designated mynA-D or csaA-D [16–18]. The repeating units are O-acetylated mainly at position C3 and sometimes at position C4 [17]. …”

Section: Introductionmentioning

confidence: 99%

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Spontaneous point mutations in the capsule synthesis locus leading to structural and functional changes of the capsule in serogroup A meningococcal populations

Ispasanie

Micoli²,

Lamelas

et al. 2018

Virulence

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Whole genome sequencing analysis of 100 Neisseria meningitidis serogroup A isolates has revealed that the csaABCD-ctrABCD-ctrEF capsule polysaccharide synthesis locus represents a spontaneous point mutation hotspot. Structural and functional properties of the capsule of 11 carriage and two disease isolates with non-synonymous point mutations or stop codons in capsule synthesis genes were analyzed for their capsular polysaccharide expression, recognition by antibodies and sensitivity to bactericidal killing. Eight of eleven carriage isolates presenting capsule locus mutations expressed no or reduced amounts of capsule. One isolate with a stop codon in the O-acetyltransferase gene expressed non-O-acetylated polysaccharide, and was not recognized by anti-capsule antibodies. Capsule and O-acetylation deficient mutants were resistant to complement deposition and killing mediated by anti-capsular antibodies, but not by anti-lipopolysaccharide antibodies. Two capsule polymerase mutants, one carriage and one case isolate, showed capsule over-expression and increased resistance against bactericidal activity of both capsule- and lipopolysaccharide-specific antibodies. Meningococci have developed multiple strategies for changing capsule expression and structure, which is relevant both for colonization and virulence. Here we show that point mutations in the capsule synthesis genes substantially contribute to the repertoire of genetic mechanisms in natural populations leading to variability in capsule expression.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spontaneous point mutations in the capsule synthesis locus leading to structural and functional changes of the capsule in serogroup A meningococcal populations

Ispasanie

Micoli²,

Lamelas

et al. 2018

Virulence

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“…where mass TSP is constant (0.069 mg); molecular weight of TSP=172.23 g/mol; Met., metabolite; N TSP , the number of protons of TSP (9 1 H) and N Met , the number of protons in the respective metabolite (26).…”

Section: Quantification Of Metabolitesmentioning

confidence: 99%

Live-cell high resolution magic angle spinning magnetic resonance spectroscopy for in vivo analysis of Pseudomonas aeruginosa metabolomics

et al. 2013

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Abstract. Pseudomonas aeruginosa (PA) is a pathogenic gram-negative bacterium that is widespread in nature, inhabiting soil, water, plants and animals. PA is a prevalent cause of deleterious human infections, particularly in patients whose host defense mechanisms have been compromised. Metabolomics is an important tool used to study host-pathogen interactions and to identify novel therapeutic targets and corresponding compounds. The aim of the present study was to report the metabolic profile of live PA bacteria using in vivo high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance spectroscopy (NMR), in combination with 1-and 2-dimensional HRMAS NMR. This methodology provides a new and powerful technique to rapidly interrogate the metabolome of intact bacterial cells and has several advantages over traditional techniques that identify metabolome components from disrupted cells. Furthermore, application of multidimensional HRMAS NMR, in combination with the novel technique total through-Bond correlation Spectroscopy (TOBSY), is a promising approach that may be used to obtain in vivo metabolomics information from intact live bacterial cells and can mediate such analyses in a short period of time. Moreover, HRMAS 1 H NMR enables the investigation of the associations between metabolites and cell processes. In the present study, we detected and quantified several informative metabolic molecules in live PA cells, including N-acetyl, betaine, citrulline, alanine and glycine, which are important in peptidoglycan synthesis. The results provided a complete metabolic profile of PA for future studies of PA clinical isolates and mutants. In addition, this in vivo NMR biomedical approach might have clinical utility and should prove useful in gene function validation, the study of pathogenetic mechanisms, the classification of microbial strains into functional/clinical groups, the testing of anti-bacterial agents and the determination of metabolic profiles of bacterial mutants. IntroductionPseudomonas aeruginosa (PA) is a ubiquitous Gram-negative bacterium that inhabits a wide array of natural environments. This bacterium is of significant clinical interest as it is a multi-antibiotic-resistant human pathogen associated with hospital-acquired infections (1,2) and a major cause of morbidity and mortality in cystic fibrosis (CF) patients. It commonly colonizes the lower respiratory and gastrointestinal tracts and the mucosa and skin of hospital patients. The establishment of chronic PA respiratory infections requires a complex adaptive process that mediates essential physiological changes that allow bacterial cells to survive and persist in the host environment. Bacteria secrete small molecules that act as specific signals to positively regulate specialized processes (3), including the production of virulence factors that mediate pathogenic infection, host colonization and the promotion of interspecies microbial interactions (4).Bacterial cell walls are complex, consisting of integrated macromolecules including c...

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The Genus Neisseria

Bennett¹,

Bratcher²,

Brehony³

et al. 2014

The Prokaryotes

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The Neisseria meningitidis Serogroup A Capsular Polysaccharide O-3 and O-4 Acetyltransferase

Cited by 48 publications

References 59 publications

Spontaneous point mutations in the capsule synthesis locus leading to structural and functional changes of the capsule in serogroup A meningococcal populations

Spontaneous point mutations in the capsule synthesis locus leading to structural and functional changes of the capsule in serogroup A meningococcal populations

Live-cell high resolution magic angle spinning magnetic resonance spectroscopy for in vivo analysis of Pseudomonas aeruginosa metabolomics

The Genus Neisseria

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