Feroze A. Ganaie, United States of America

University of Alabama at Birmingham Medicine

Presenter of 1 Presentation

ORAL STREPTOCOCCI: A SOURCE OF NEW AND VIRULENT CAPSULE FOR PNEUMOCOCCI (ID 244)

Abstract

Background

Pneumococcal conjugate vaccines have been very successful, but their use has increased infections by non-vaccine serotypes. Oral streptococci often harbor capsular polysaccharide (PS) synthesis loci (cps). If pneumococcus can replace its cps with oral streptococcal cps, it may increase its serotype repertoire.

Methods

Chemical structures of capsular PS from an oral streptococcus strain, SK95, and a pneumococcal strain, D39, were determined by 2-dimensional NMR. An acapsular pneumococcus strain was transformed with cps from SK95 and D39, which were compared for their virulence by measuring non-specific phagocytic killing and their ability to kill mice.

Results

SK95 and D39 both produce structurally identical type 2 capsules. Baby rabbit serum (BRS) at 10% non-specifically killed >50% of SK95; however, 12·5% BRS killed <20% of D39. Non-encapsulated pneumococci became resistant to BRS as D39 following transformation with SK95 cps. Similarly, SK95 is avirulent in well-established in vivo mouse model. When the acapsular pneumococcus was transformed with SK95 cps, the transformant became virulent and killed all mice.

Conclusions

Oral streptococcus cps can make acapsular pneumococcus virulent and inter-species cps transfer should be considered a potential mechanism for serotype replacement. Our findings highlight potential limitations of current WHO criterion for studying serotypes of pneumococci carried without first isolating bacteria.

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Author Of 2 Presentations

DISCOVERY OF A NOVEL PNEUMOCOCCAL CAPSULE TYPE WITHIN SEROGROUP 24 (ID 818)

Abstract

Background

Pneumococcal capsules are important in pathogenesis and vaccine development. Serotype 24F capsule consists of a hexasaccharide repeating unit with arabinitol (WO 2019/050815 AI). Here, we describe the discovery of a novel serotype (“24X”) within serogroup 24.

Methods

Serological properties of pneumococcal isolates were studied using Quellung. Serotypes 24F, 24A, 24B and 24X were subjected to whole genome sequencing (WGS). The capsular polysaccharide (CPS) structures were elucidated by NMR and GC-MS.

Results

Multiple pneumococcal isolates from several countries reacted with both factor sera 24d and 24e. Since this reaction pattern has not been reported and is unique, the isolates were provisionally labelled to be serotype “24X.” Genetic studies of cps loci could not distinguish 24X from 24F or 24B. Chemical structure studies of serogroup 24 members showed that 24B CPS is like 24F except for having ribitol instead of arabinitol, 24X CPS contains both repeat units of 24F and 24B. These findings could explain their reactivity with factor sera 24d and 24e.

Conclusions

The 24X capsule has a distinct serology and repeating unit structure, which qualify it as a new serotype. According to the Danish naming system, 24X was named serotype 24C. Correlation of cps loci with the capsule structure is under investigation.

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ORAL STREPTOCOCCI: A SOURCE OF NEW AND VIRULENT CAPSULE FOR PNEUMOCOCCI (ID 244)

Abstract

Background

Pneumococcal conjugate vaccines have been very successful, but their use has increased infections by non-vaccine serotypes. Oral streptococci often harbor capsular polysaccharide (PS) synthesis loci (cps). If pneumococcus can replace its cps with oral streptococcal cps, it may increase its serotype repertoire.

Methods

Chemical structures of capsular PS from an oral streptococcus strain, SK95, and a pneumococcal strain, D39, were determined by 2-dimensional NMR. An acapsular pneumococcus strain was transformed with cps from SK95 and D39, which were compared for their virulence by measuring non-specific phagocytic killing and their ability to kill mice.

Results

SK95 and D39 both produce structurally identical type 2 capsules. Baby rabbit serum (BRS) at 10% non-specifically killed >50% of SK95; however, 12·5% BRS killed <20% of D39. Non-encapsulated pneumococci became resistant to BRS as D39 following transformation with SK95 cps. Similarly, SK95 is avirulent in well-established in vivo mouse model. When the acapsular pneumococcus was transformed with SK95 cps, the transformant became virulent and killed all mice.

Conclusions

Oral streptococcus cps can make acapsular pneumococcus virulent and inter-species cps transfer should be considered a potential mechanism for serotype replacement. Our findings highlight potential limitations of current WHO criterion for studying serotypes of pneumococci carried without first isolating bacteria.

Hide