Abstract
Acinetobacter baumannii isolate NIPH 329 carries a novel capsular polysaccharide (CPS) gene cluster, designated KL46, that is closely related to the KL5 locus in A. baumannii isolate SDF but includes genes for synthesis of 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-non-2-ulosonic (di-N-acetylpseudaminic) acid (Pse5Ac7Ac) instead of the corresponding D-glycero-D-galacto isomer (di-N-acetyllegionaminic acid) (Leg5Ac7Ac). In agreement with the genetic content of KL46, chemical studies of the K46 CPS produced by NIPH 329 revealed a branched tetrasaccharide repeat (K unit) with an overall structure the same as K5 from SDF but with â-Pse5Ac7Ac replacing α-Leg5Ac7Ac. As for K5, the K46 unit begins with d-GalpNAc and includes α-d-GlcpNAc-(1→3)-d-GalpNAc and α-d-Galp-(1→6)-d-GlcpNAc linkages, formed by Gtr14 and Gtr15 glycosyltransferases, respectively. The Gtr94K46 glycosyltransferase, which is related to Gtr13K5, links Pse5Ac7Ac to d-Galp in the growing K unit via a â-(2→6) linkage. Nearly identical Wzy enzymes connect the K46 and K5 units via a α-D-GalpNAc-(1→3)-α-D-Galp linkage to form closely related CPSs. Both Pse5Ac7Ac in K46 and Leg5Ac7Ac in K5 are acetylated at O4 but no acetyltransferase gene is present in KL46 or KL5. Related acetyltransferases were found encoded in the NIPH 329 and SDF genomes, but not in other strains carrying an unacetylated Pse or Leg derivative in the CPS. The genes encoding the acetyltransferases were in different putative phage genomes. However, related acetyltransferases were rare among the >3000 publically available genome sequences.
Highlights
Capsular polysaccharide (CPS) is an essential virulence determinant for the globally-significant bacterial pathogen, Acinetobacter baumannii, which has been listed by the World Health Organisation as the leading critical priority pathogen for therapeutics development due to the increasing prevalence of isolates with limited treatment options [1]
The KL46 gene cluster (Fig 1A) has an arrangement that is typical for A. baumannii K locus (KL) gene clusters [2] in that it includes a module of genes for capsular polysaccharide (CPS) export and another one for synthesis of simple sugars on either side of a central region that is specific to the K46 CPS
The K46 CPS structure elucidated in this study includes a 4-O-acetylated variant of pseudaminic acid attached as a side chain to a a-D-Galp-(1!6)-a-D-GlcpNAc-(1!3)-D-GalpNAc backbone via a a-(2!6) linkage to D-Galp
Summary
Capsular polysaccharide (CPS) is an essential virulence determinant for the globally-significant bacterial pathogen, Acinetobacter baumannii, which has been listed by the World Health Organisation as the leading critical priority pathogen for therapeutics development due to the increasing prevalence of isolates with limited treatment options [1]. As the outer-most antigenic component of the cell, the CPS has been exploited in various vaccine approaches and novel phage therapies. These strategies have challenges due to the extreme variation of the CPS structures in different isolates; more than 125 distinct CPS biosynthesis gene clusters have been identified (J.J. Kenyon, unpublished data) at the genomic K locus (KL) that directs the synthesis of the CPS [2]. The CPS of different isolates may have different sugar compositions and include different linkages between these sugars or between oligosaccharide repeats (K units) that make up the CPS polymers extending from the cell surface (e.g. [3,4,5,6,7,8])
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