5,7-Di-N-acetyl-8-epiacinetaminic acid: A new non-2-ulosonic acid found in the K73 capsule produced by an Acinetobacter baumannii isolate from Singapore

Kenyon, Johanna J.; Notaro, Anna; Hsu, Li Yang; Castro, Cristina De; Hall, Ruth M.

doi:10.1038/s41598-017-11166-4

Cited by 30 publications

(21 citation statements)

References 15 publications

(28 reference statements)

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“…A panel of 21 A. baumannii strains were used covering a range of 22 different bacterial capsule types (K1 to K3, K9, K11, K15, K30, K33, K35, K37, K40, K43 to K49, K57, K73, and K83) ( Table 3). They mostly belong to the collections of Alexandr Nemec (NIPH and ANC strains) and of the Institut Pasteur (CIP strains) (39)(40)(41)(42)(43)(44)(45)(46)(47). All strains were routinely grown at 37°C in Trypticase soy broth (TSB) or in Trypticase soy agar (TSA; 1.5% [wt/vol] agar).…”

Section: Methodsmentioning

confidence: 99%

Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

Oliveira

Costa

Ferreira

et al. 2019

J Virol

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Acinetobacter baumannii is an important pathogen causative of health care-associated infections and is able to rapidly develop resistance to all known antibiotics, including colistin. As an alternative therapeutic agent, we have isolated a novel myovirus (vB_AbaM_B9) which specifically infects and makes lysis from without in strains of the K45 and K30 capsule types, respectively. Phage B9 has a genome of 93,641 bp and encodes 167 predicted proteins, of which 29 were identified by mass spectrometry. This phage holds a capsule depolymerase (B9gp69) able to digest extracted exopolysaccharides of both K30 and K45 strains and remains active in a wide range of pH values (5 to 9), ionic strengths (0 to 500 mM), and temperatures (20 to 80°C). B9gp69 was demonstrated to be nontoxic in a cell line model of the human lung and to make the K45 strain fully susceptible to serum killing in vitro. Contrary to the case with phage, no resistance development was observed by bacteria targeted with the B9gp69. Therefore, capsular depolymerases may represent attractive antimicrobial agents against A. baumannii infections. IMPORTANCE Currently, phage therapy has revived interest for controlling hard-to-treat bacterial infections. Acinetobacter baumannii is an emerging Gram-negative pathogen able to cause a variety of nosocomial infections. Additionally, this species is becoming more resistant to several classes of antibiotics. Here we describe the isolation of a novel lytic myophage B9 and its recombinant depolymerase. While the phage can be a promising alternative antibacterial agent, its success in the market will ultimately depend on new regulatory frameworks and general public acceptance. We therefore characterized the phage-encoded depolymerase, which is a natural enzyme that can be more easily managed and used. To our knowledge, the therapeutic potential of phage depolymerase against A. baumannii is still unknown. We show for the first time that the K45 capsule type is an important virulence factor of A. baumannii and that capsule removal via the recombinant depolymerase activity helps the host immune system to combat the bacterial infection.

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Section: Methodsmentioning

confidence: 99%

Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

Oliveira

Costa

Ferreira

et al. 2019

J Virol

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“…Alternatively the variation may be striking, such as the incorporation of rare sugars including pseudaminic, legionaminic, or acinetaminic acid derivatives as seen in K2/6, K49, and K12/13 structures, respectively (Figure 2) (Kenyon et al, 2014a, 2015; Vinogradov et al, 2014; Kasimova et al, 2018). Interestingly, acinetaminic acid derivatives have only been identified in A. baumannii and are found nowhere else in nature (Kenyon et al, 2017). Additionally, some K units incorporate unique derivatives of specific glycans, for instance the pseudaminic acid of K93 is acetylated with a ( R )-3-hydroxybutanoyl group (Kasimova et al, 2017), whereas in K2 and K6 the pseudaminic acid is non-acetylated (Figure 2).…”

Section: Cps Structuresmentioning

confidence: 99%

Diversity and Function of Capsular Polysaccharide in Acinetobacter baumannii

2019

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The Gram-negative opportunistic bacterium Acinetobacter baumannii is a significant cause of hospital-borne infections worldwide. Alarmingly, the rapid development of antimicrobial resistance coupled with the remarkable ability of isolates to persist on surfaces for extended periods of time has led to infiltration of A. baumannii into our healthcare environments. A major virulence determinant of A. baumannii is the presence of a capsule that surrounds the bacterial surface. This capsule is comprised of tightly packed repeating polysaccharide units which forms a barrier around the bacterial cell wall, providing protection from environmental pressures including desiccation and disinfection regimes as well as host immune responses such as serum complement. Additionally, capsule has been shown to confer resistance to a range of clinically relevant antimicrobial compounds. Distressingly, treatment options for A. baumannii infections are becoming increasingly limited, and the urgency to develop effective infection control strategies and therapies to combat infections is apparent. An increased understanding of the contribution of capsule to the pathobiology of A. baumannii is required to determine its feasibility as a target for new strategies to combat drug resistant infections. Significant variation in capsular polysaccharide structures between A. baumannii isolates has been identified, with over 100 distinct capsule types, incorporating a vast variety of sugars. This review examines the studies undertaken to elucidate capsule diversity and advance our understanding of the role of capsule in A. baumannii pathogenesis.

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“…Other members of the class include acinetaminic acid 4 and fusaminic acid 5 (Figure 1), and the 4- and 8-epimers of legionaminic acid (not shown). 23,24,52–55…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

Dhakal

Crich

2018

J. Am. Chem. Soc.

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Pseudaminic acid is an amino deoxy sialic acid whose glycosides are essential components of many pathogenic Gram-negative bacterial cell walls including those from Pseudomonas aeruginosa, Vibrio cholerae, Campylobacter jejuni, Campylobacter coli, Vibrio vulnificus, and Pseudoalteromonas distincta. The study of pseudaminic acid glycosides is however hampered by poor availability from nature, the paucity of good synthetic methods, and limited to no understanding of the factors controlling stereoselectivity. Conformational analysis of the side chains of various stereoisomeric sialic acids suggested that the side chain of pseudaminic acid would take up the most electron-withdrawing trans,gauche-conformation, as opposed to the gauche,gauche conformation of N-acetyl neuraminic acid and the gauche,trans-conformtion of 7-epi N-acetyl neuraminic acid, leading to the prediction of high equatorial selectivity. This prediction is borne out by the synthesis of a suitably protected pseudaminic acid donor from N-acetyl neuraminic acid in 20 steps and 5% overall yield, and by the exquisite equatorial selectivity it displays in coupling reactions with typical glycosyl acceptors. The selectivity of the glycosylation reactions is further buttressed by the development and implementation of conditions for the regioselective release of the two amines from the corresponding azides, such as required for the preparation of the lipopolysaccharides. These findings open the way to the synthesis and study of pseudaminic acid-based bacterial lipopolysaccharides and, importantly in the broader context of glycosylation reactions in general, underline the significant role played by side chain conformation in the control of reactivity and selectivity.

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5,7-Di-N-acetyl-8-epiacinetaminic acid: A new non-2-ulosonic acid found in the K73 capsule produced by an Acinetobacter baumannii isolate from Singapore

Cited by 30 publications

References 15 publications

Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

Diversity and Function of Capsular Polysaccharide in Acinetobacter baumannii

Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

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