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Determining the epidemiology and molecular evolution of antimicrobial drug resistance in Cape Verde

Primary Supervisor: Sandra Beleza, Department of Genetics and Genome Biology

Secondary Supervisor: Professor Marco R. Oggioni, Department of Genetics and Genome Biology

PhD project title: Determining the epidemiology and molecular evolution of antimicrobial drug resistance in Cape Verde

University of Registration: University of Leicester

Project outline: 

Cape Verde is an archipelago located 450 km off the coast of Senegal, that was found uninhabited by the Portuguese in the mid-15th century. The southern islands were populated first with European immigrants and enslaved Africans from the neighbouring coast. Two centuries later, after the decline of the slave trade, there was a movement of people towards the islands of the north. Due to its geographic isolation, unique history of colonisation (serial founder effects), strong communication with other countries through recent migration and tourism, and finally, a dry climate that prevents the spread of major tropical disease, the archipelago of Cape Verde provides a unique model for the study of the natural history of infectious disease and evolution of antimicrobial drug resistance (AMR) caused by microorganisms that are widespread across the world. We have established two funded research programmes in these areas. The first project aims to study the epidemiology and genomics of host-pathogen interactions underlying susceptibility to the stomach–colonizing bacterium Helicobacter pylori. H. pylori infection is the most common infection in the world and causes peptic ulcer and gastric cancer; gastric cancer is the second cause of death from malignancy. Preliminary results from our work indicate that the prevalence of infection in the general population is ~84%, and that the bacterial genomes derive ancestry from both European and African continents. The level of AMR of the strains collected to four antibiotics is high and we observed cases of multidrug resistance. We also observe multiple infections within the same host, which differ in the antibiotic resistance pattern: there are both susceptible and resistance strains inhabiting the same stomach.

In the second project, we collated data on AMR between 2013 and 2017 from the records of the Northern and Southern central hospitals in Cape Verde. We observed an increase in resistance levels of Staphylococcus aureus strains throughout the years across the archipelago in Cape Verde. S. aureus is a common colonizer of the anterior nares of the nose, the skin and of other mucosa; but S. aureus strains can cause important infections in the community and in the hospital. We have found a lineage in S. aureus with a unique pattern of antibiotic resistance.

 

To evaluate the origin and molecular evolution of AMR in H. pylori and S. aureus in Cape Verde, we have obtained whole-genome sequences of both susceptible and resistant strains. The specific objectives are:

  1. To perform genome-wide association analyses to identify new genetic variants and genes associated with differences of susceptibility to antibiotics in pylori. The resistance patterns observed are not fully explained by resistance variants already described. The dataset composed by >220 sequenced strains characterized for antibiotic resistance levels will allow to perform phenotype-genotype correlations and to evaluate the genetic architecture of AMR in H. pylori in Cape Verde.
  2. To identify the genetic elements that give rise to both the common and unique pattern of antibiotic resistance in aureus in Cape Verde. To annotate known genetic variants of resistance and to perform genome-wide analyses of the diversity of the resistant strains.
  3. To evaluate the genetic diversity and evolution of pylori and S. aureus strains across the Cape Verde. To characterize the genetic variation and to perform population genetics analyses in both susceptible and resistant strains to evaluate the role of the population history (serial founder effects) of the archipelago and of the action of the antibiotic selective pressure in the distribution of the genetic diversity of H. pylori and S. aureus strains across the archipelago.
  4. To understand within-the-host evolution of AMR in H. pylori. To characterize the genetic variation and to perform population genetics analyses of strains with different AMR patterns colonizing the same stomach.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

    Techniques that will be undertaken during the project:

    The project involves mostly computational, evolutionary (phylogenetics and population genetics) and statistical analyses. It will also include microbial techniques (bacterial isolation and culture, tests for antimicrobial drug susceptibility), molecular genetics (e.g. DNA extraction, DNA library construction, PCR), and NGS using paired-end sequencing. The candidate will also have the opportunity to conduct fieldwork in Cape Verde, although this is not really a requirement.

    Contact: Dr Sandra Beleza, University of Leicester