Insertion Sequence
 1515
 in the
 ply
 Gene of a Type 1 Clinical Isolate of
 Streptococcus pneumoniae
 Abolishes Pneumolysin Expression

Garnier, Fabien; Chiu, Cheng-Hsun; Charpentier, Emmanuelle; Masson, Geoffrey; Grelaud, C; Stach, Jean Francois; Denis, François; Ploy, Marie-Cécile

doi:10.1128/jcm.02168-06

Cited by 10 publications

(12 citation statements)

References 10 publications

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“…Intriguingly, lineages A and C were reported to exhibit residual or no haemolytic activity, attributed to the expression of a non-haemolytic variant of pneumolysin (Ply) or to its null expression 8 , 18 , 19 . Given the critical role attributed to Ply and its haemolytic activity in enhancing pathogenicity, we raised the question as to whether common mechanisms and/or unknown virulence factor(s) may have compensated for the loss of haemolytic activity, which allowed both lineages A and C to thrive as invasive isolates 20 . In the present study, we sought to understand the virulence properties of these two lineages, using ST306 and ST615 as their respective representatives.…”

Section: Introductionmentioning

confidence: 99%

Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity

Panagiotou

Chaguza

Yahya

et al. 2020

Sci Rep

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Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.

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Section: Introductionmentioning

confidence: 99%

Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity

Panagiotou

Chaguza

Yahya

et al. 2020

Sci Rep

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“…It is possible that another, possibly undiscovered, virulence factor has made the hemolytic activity of pneumolysin redundant in these organisms. This hypothesis is supported by the identification of an invasive serotype 1 organism with entirely absent pneumolysin expression [103].…”

Section: Other Virulence Factorsmentioning

confidence: 95%

What is Different About Serotype 1 Pneumococci?

Ritchie

Mitchell

Evans³

2011

Future Microbiol.

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Serotype 1 Streptococcus pneumoniae is among the most commonly isolated serotype in invasive pneumococcal disease but is rarely found causing asymptomatic nasopharyngeal colonization. Compared to infection by other serotypes, infection caused by serotype 1 is more likely to be identified in young patients without comorbidities but is generally associated with a lower mortality. Empyema and extrapulmonary manifestations are common. Outbreaks of serotype 1 disease have been reported in closed communities and epidemics are particularly common in sub-Saharan Africa. The serotype 1 capsular polysaccharide is a zwitterionic structure that enables it to function as a T-cell dependent antigen under some circumstances, in contrast to other pneumococcal capsular polysaccharides that are T-cell independent antigens. There are also differences in the key virulence factor pneumolysin in some serotype 1 isolates. The clinical significance of these differences remains to be determined.

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“…pneumoniae expressing PLY with defined mutations that affect cytolytic and complement-activating properties have reduced virulence compared to that of WT pneumococci (9,10,37). Though the amino acid sequence of PLY had been thought to be well conserved throughout pneumococcal serotypes (46), it has lately become clear that some clinical isolates bear mutations in their PLY genes (28,35,41,44). Some of these mutations affect the hemolytic activity of PLY and are most commonly found in isolates of serotypes 1 and 8 (35,41,44).…”

Section: Discussionmentioning

confidence: 99%

Pneumolysin Released duringStreptococcus pneumoniaeAutolysis Is a Potent Activator of Intracellular Oxygen Radical Production in Neutrophils

et al. 2008

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Streptococcus pneumoniae is a major cause of otitis media, pneumonia, meningitis, and septicemia in humans. The host defense against this pathogen largely depends on bacterial killing by neutrophils. A peculiar property of pneumococci is their tendency to undergo autolysis, i.e., autoinduced disruption of the bacterial cell wall mediated by activation of the enzyme LytA, under stationary growth conditions. LytA is a virulence factor, but the molecular background for this has not been fully clarified. Here we examine how bacterial compounds released upon autolysis affect the production of reactive oxygen species (ROS) in neutrophils. We found that the S. pneumoniae strains A17 and D39 induced activation of the NADPH oxidase and the production of ROS in human neutrophils and that this activation was blocked when LytA was inactivated. The ROS-inducing bacterial substance released from autolyzed bacteria was identified as the cytoplasmic toxin pneumolysin. Further screening of clinical pneumococcal strains of various sero-and genotypes revealed that selected strains expressing toxins with reduced pneumolysin-dependent hemolytic activity had decreased abilities to induce ROS in neutrophils. Furthermore, a mutated form of purified pneumolysin lacking hemolytic and complement binding functions (PdT) did not induce any oxygen radical production. The ROS produced in response to pneumolysin formed mainly intracellularly, which may explain why this production was not detected previously. ROS released intracellularly may function as signaling molecules, modifying the function of neutrophils in bacterial defense.

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Insertion Sequence 1515 in the ply Gene of a Type 1 Clinical Isolate of Streptococcus pneumoniae Abolishes Pneumolysin Expression

Cited by 10 publications

References 10 publications

Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity

Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity

What is Different About Serotype 1 Pneumococci?

Pneumolysin Released duringStreptococcus pneumoniaeAutolysis Is a Potent Activator of Intracellular Oxygen Radical Production in Neutrophils

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