Student Awarded

Tinashe Kenny Nyazika

Tinashe Kenny Nyazika

Country: Malawi

Project Title: Investigating evidence for potential survival of Streptococcus

Institution: Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW)

In this project, I will be investigating whether the bacteria known as pneumococcus is able to survive inside alveolar macrophages (AMs) or not. AMs are important cells in lung and are the chief resident phagocytes responsible for killing and clearing extracellular bacterial pathogens such as pneumococcus. This work is part of a collaborative study between Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) and the University of Leicester. We will collect bronchoalveolar lavages (BAL) fluid from 90 asymptomatic individuals as part of the ongoing project at MLW. The AMs present in the BAL samples will be experimentally infected with pneumococcus serotype 3 or naturally-infected with pneumococcus from their hosts. These cells will then be fixed and prepared for confocal microscopy and electron microscopy in Malawi (MLW lab) and shipped to University of Leicester where I will do the microscopy analyses. Furthermore, we will try to describe cellular compartments associated with survival of pneumococcus within AMs. This work is important as it will give us insights of the mechanisms and the kinetics behind the increased risk of pneumococcal pneumonia in HIV-infected individuals.

African Supervisor

Kondwani Jambo

Kondwani Jambo

African Host Country: Malawi

Institution: Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Laboratory: Viral Immunology Group

The group’s main focus is investigating immune responses against viral infections and understanding how viral infections modulate host immunity in the mucosa.  The group has mainly focused on characterising HIV-mediated perturbations in the lung, and how these impact host immunity against common respiratory pathogens, including Streptococcus pneumoniae, Mycobacterium tuberculosis and Influenza virus, in low-income settings. We have shown that HIV-mediated perturbations in the lung are extensive, are not completely restored by antiretroviral therapy (ART), and that HIV persists in the lung of ART-treated aviremic patients. The group’s interest now includes defining the mechanisms of HIV persistence in the mucosal tissues (lung and gut) in ART-treated aviremic patients, with the goal of gaining insights to inform novel HIV cure strategies. In addition, the group also has growing interest in early immune development, especially in understanding how neonatal immune profiles impact vaccine responses and clinical outcomes later in life.

International Supervisor

Marco Rinaldo Oggioni

International Host Country: United Kingdom

Institution: University of Leicester

Laboratory: Department of Genetics and Genome Biology

The group has two main areas of interests:

  1. Analysis of virulence mechanisms of pneumococci, by use of genomic tools, study of microbial physiology, set up of novel in vitro models including biofilms and in vivo infection models. The main scope is the recognition of specific phases characterising microbial physiology during infection with the aim of identification of novel drug targets. In this context, my group focuses on carbon metabolism of the bacterium, both in vitro and within the host, with the idea that the ‘behaviour’ of the bacterium is largely influenced by their metabolism and that nutrient availability in different niches within the host govern important aspects in host pathogen interaction.
  2. My group has described pneumococci as being capable of replicating in a subset of splenic macrophages prior starting invasive disease in mice, with invasive disease being prevented by blocking intracellular replication (Ercoli et al., Nature Microbiology 2018). In order to explore the validity of these findings an ex vivo perfusion model for porcine spleens was developed and intracellular replication of pneumococci could be confirmed (Chung et al., ALTEX 2019). Recently, MRO was awarded as Chief Investigator by the Health Research Authority to use human spleens in ex vivo perfusion models. This work is now providing the first functional analysis of the roles of specific macrophage subsets in the human spleen during the first phases of infection. This innovative work holds promise to rewrite some of the concepts of the pathogenesis of infection and the rational for antimicrobial drug treatment.