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Streptococcus

Streptococcal infections are any type of infection caused by the group of bacteria Streptococcus. There are many different types of Streptococci and infections vary in severity from mild throat infections to life-threatening conditions such as meningitis or pneumonia.

Streptococcus Pneumoniae

Nasal pneumococcal carriage

Colonisation of the nasopharynx is common, particularly in the developing world where incidence of invasive disease is also high. Understanding the bacterial and host immune conditions by which pathogens such as Streptococcus pneumoniae are carried in the nasopharynx is key to elucidating the complex relationship between bacteria and host. As part of this, we are interested in host immune regulation of carriage and bacterial factors that contribute to this (funded by MRC Programme Grant). In addition, bacterial host to host transmission and how invasive disease develops following transmission and carriage are areas of research interest (funded by JPI-AMR).

The role of T cells in carriage and pneumonia

T regulatory cells play a key role in the modulation of immune responses to pneumococcal infection. In the lung, these cells prevent pathological inflammation by limiting the production of pro inflammatory cytokines (PLoS Pathog. 2012;8(4):e1002660). Emerging evidence suggests that T regulatory cell activity is also required for the establishment and maintenance of pneumococcal carriage in the nasopharynx (Am J Respir Crit Care Med. 2014 May 15;189(10):1250-9.) Current work aims to elucidate the interactions between T regulatory cells and other components of host immunity during pneumococcal infection.

The role of capsule in carriage

Even though the pneumococcus is commonly found in nasopharyngeal carriage, there are some serotypes that are not associated with carriage. Streptococcus pneumoniae serotype-1 is one of the main causes of pneumococcal invasive disease, particularly in sub-Saharan Africa, but it is rarely found in nasopharyngeal carriage. Since nasopharyngeal carriage is a precursor to disease we would like to understand how serotype-1 causes disease, why it behaves in a different way to other pneumococcal serotypes and how it evades host immunity. As part of this effort, we are also interested in non-typeable serotypes and their role in colonisation and interaction with other bacterial strains as well as with host immunity.

Environmental factors and susceptibility to carriage and invasive pneumococcal disease

Heat exposure is a significant risk factor in causing pneumococcal disease. In Sub-Saharan Africa, spikes in the incidence of pneumococcal meningitis cases have been linked to high temperatures and exposure to airborne dust, especially in the so-called Meningitis Belt.  We described the mechanism behind this (JAllergyClinImmunol.doi: 10.1016/j.jaci.2016.04.062). Similarly, we have also factors such as diesel particles (JAllergyClinImmunol. doi: 10.1016/j.jaci.2019.11.039) and e-cigarette vapours (EurRespirJ. doi: 10.1183/13993003.01592-2017) can raise the risk of pneumococcal invasive diseases. We are further investigating the molecular basis behind these observations.

Streptococcus agalactiae

Carriage-to-invasive disease mechanism

Streptococcus agalactiae (also known as Group B Streptococcus, GBS) is a Gram-positive bacterium and the most leading cause of invasive disease in newborns. GBS asymptotically colonise the gastrointestine and lower genital tract of 20-30% of healthy adults. GBS can transmitted from colonise pregnant women to the newborn in utero through ascending infection or during birth causing life-threatening disease such as sepsis, pneumonia and meningitis. In this project, we seek to further understand the mechanisms by which GBS colonises the vaginal tract during pregnancy and to characterise the associated host immune response. Our study involves the use of an array of molecular genetic approaches as well as in vitro assays and in vivo models to identify bacterial virulence determinants and host factors that contribute to GBS disease progression.

Streptococcus pyogenes

Investigating the pathogenesis of GAS infection

Streptococcus pyogenes also known as Group A Streptococcus (GAS) is among the most diverse of any human pathogen, and has a varied range of clinical manifestations. GAS causes mild superficial infections such as pharyngitis and serious invasive infections such as necrotising fasciitis. Our most recent study focused on an outbreak of invasive GAS infections in Liverpool, Merseyside that had a mortality rate of 29%. Following sequencing, clinical GAS isolates from the outbreak were determined as a new emm 32.2 strain (J Clin Microbiol. 2017 Jun;55(6):1837-1846). There are two main objectives of this study; first to use in vitro methods to assess the differences between the outbreak emm 32.2 strain and other contemporaneous circulating sequence types (invasive and carriage) and secondly, to set up animal models to investigate the pathogenesis of different clinical syndromes in vivo. This included developing a novel model of septic arthritis to look closely at the mechanism of disease and immunopathogenesis (Sci Rep. 2021 Sep 24;11(1):19011.)