Marcus Leung: project summary, publications and presentations
Title of project
Multiple colonization of Streptococcus pneumoniae as means of cell-to-cell communication and adaptive microevolution.
Streptococcus pneumoniae is among the leading bacterial agents of otitis media, pneumonia, bacteraemia, and meningitis in children under the age of 5. Despite the wide spectrum of diseases manifestations, the pneumococcus commonly resides in the nasopharyngeal tract of asymptomatic hosts. Critical to its success in survival during colonization is rapid adaptation in response to host defenses and chemotherapeutics. The primary mechanism for adaptation in S. pneumoniae is homologous recombination with exogenous DNA, which may ultimately result in the acquisition of beneficial genes and alleles. Thus, other bacteria sharing its habitat, particularly other pneumococci will expand the gene pool available for uptake, some of which would confer adaptive benefits.
The research aim was to design a novel serotyping method for pneumococcal characterization, and analyze multiple colonization of a cohort of children residing in rural Tanzania. The conventional serotyping of more than 90 types of pneumococci is expensive and time-consuming, in addition to false-positives. Current molecular alternatives include multiplex and multistep PCR. We have developed a novel DNA-based typing method that utilizes a single universal primer pair that is able to detect up to 50 different serotypes, including serotypes most commonly detected in carriage and diseases in the United Kingdom, as well as ones covered in the latest 13-valent conjugate vaccines. We have confirmed that this method does not require a culture step, and has a high species specificity and sensitivity. This novel typing method would provide a promising alternative to serological identification of S. pneumoniae in routine clinical laboratories
Understanding the extent of pneumococcal diversity present within a single host, as this will provide insight as to the supragenome size available for horizontal gene transfer. Multiple isolates from each pneumococcal colonization event were genotyped, serotyped and antibiotyped for penicillin and co-trimoxazole. A 12-month longitudinal study was undertaken on 21 healthy Tanzanian children. We have detected extensive diversity of strains co-colonizing. Results from this work was recently accepted into publication in Infection Genetics and Evolution, currently in publishing stage.
Charalambous BM, Leung MH.
Pneumococcal sepsis and nasopharyngeal carriage.
Curr. Opin. Pulm. Med. 2012. In publication.
Leung MH, Oriyo NM, Gillespie SH, Charalambous BM.
The adaptive potential during nasopharyngeal colonisation of Streptococcus pneumoniae.
Infect. Genet. Evol. 2012. 11:1989-1995.
Leung MH, Gillespie SH, Charalambous BM.
Title: Molecular method of capsular typing in Streptococcus pneumoniae using only a single primer pair.
7th International Symposium on Pneumococci and Pneumococcal Diseases. Tel Aviv, Israel, 2010.
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