Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms

Chaguza, Chrispin; Yang, Marie; Jacques, Laura C.; Bentley, Stephen D.; Kadioglu, Aras

doi:10.1016/j.tim.2021.11.007

Cited by 6 publications

(5 citation statements)

References 114 publications

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“…Although a deeper understanding of its pathogenicity has emerged recently (8,34,(39)(40)(41), there is a lack of knowledge of its transmission dynamics, a key factor in the emergence of disease outbreaks.…”

Section: Discussionmentioning

confidence: 99%

“…Serotype 1 is one of the most prevalent invasive pneumococcal serotypes in West and Sub-Saharan Africa, which includes the sequence type (ST) 217 hypervirulent clonal complex (6)(7)(8)(9)(10)(11). Interestingly, despite a very low prevalence in healthy carriers (< 1-2%) (12) and a short carriage duration in humans, estimated at approximatively 9 days before clearance (13), serotype 1 is a major cause of IPD outbreaks (8,(14)(15)(16), mainly due to transmission in older children, adolescents and adults (17), suggesting that its acquisition and transmission is more transient and dynamic than other serotypes. However, the mechanisms behind serotype 1 transmission between individuals remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission

Baltazar

Audshasai

Jacques

et al. 2023

Preprint

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Streptococcus pneumoniae serotype 1 is a major cause of invasive pneumococcal disease. Despite its high attack rate, serotype 1 exhibits a low carriage prevalence within the population, which raises important questions about the relationship between carriage and transmission of hypervirulent pneumococcal strains between individuals. We compared the transmission dynamics of serotype 1 sequence type ST217 to serotype 2 strain D39 using a novel model of transmission in young adult mice. Donor index mice were intranasally infected with ST217, D39 or isogenic pneumolysin-deficient mutants and co-housed with recipient naive contact mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of shedding and nasal colonisation in index and contact mice. The role of the toxin pneumolysin in shedding, transmission and colonisation, and the host nasopharyngeal immune response were investigated. We show that ST217 was shed in index mice at significantly greater levels compared to D39. Upon viral co-infection, ST217 was shed and transmitted at a faster rate to contact mice and displayed higher transmission levels compared to D39. Interestingly, the toxin pneumolysin did not play a role in shedding. However, upon acquisition by contact mice, pneumolysin-dependent macrophage recruitment was observed in the nasopharynx. Our results show that the rapid and high transmission rate of serotype 1 is a key factor in its ability to disseminate quickly within the population and cause disease outbreaks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission

Baltazar

Audshasai

Jacques

et al. 2023

Preprint

Self Cite

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“…Serotype-1 (sequence type 217) was a clinical isolate obtained from the cerebrospinal fluid of an adult male patient, archived at the Malawi-Liverpool-Wellcome Trust Clinical Research Centre, Blantyre, Malawi. The D39 strain was chosen for its value as a well-characterized benchmark isolate, while serotype 1 was used for its relevance as a high attack rate strain, i.e., very short periods of carriage with a high incidence of invasive disease ( 126 ). Both D39 and serotype 1 strains used in this study are known to be viable in blood up to at least 48 to 72 hours when administered intravenously ( 31 , 127 ).…”

Section: Methodsmentioning

confidence: 99%

Streptococcus pneumoniae Rapidly Translocate from the Nasopharynx through the Cribriform Plate to Invade the Outer Meninges

Audshasai

Coles

Panagiotou

et al. 2022

mBio

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Using two-photon imaging, we show that pneumococci translocate from the nasopharynx to the dorsal meninges of a mouse in the absence of any bacteria found in blood or cerebrospinal fluid. Strikingly, this takes place within minutes of inhaled delivery of pneumococci, suggesting the existence of an inward flow of fluid connecting the nasopharynx to the meninges, rather than a receptor-mediated mechanism.

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“…(ST217). This serotype is a major cause of invasive pneumococcal disease globally, especially in Africa, South America, and Asia, with geographically distinct sequence types (STs) that form three genetic clusters designated as lineage A, B, and C [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

et al. 2023

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Background This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction. Methods The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework. Results Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability. Discussion Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis. Conclusion A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.

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Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms

Cited by 6 publications

References 114 publications

Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission

Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission

Streptococcus pneumoniae Rapidly Translocate from the Nasopharynx through the Cribriform Plate to Invade the Outer Meninges

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

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