On July 20th, Dr Eoin West, from the Division of Pulmonary and Critical Care at the University of Washington, gave a well-attended lunch talk titled ‘Lactoferrin as a determinant of outcome in melioidosis’.
His engaging talk was designed to be relevant to those without much background in melioidosis while still being informative to those who already work in the area. The talk started with a brief background of melioidosis and its impact. The infectious disease, now thought to be spread globally, is particularly prevalent in northeast Thailand. This is where much of Dr West’s, and others’, research has taken place. Melioidosis is a leading infectious cause of death with a mortality rate of 40%, which has sadly remained unchanged for many years.
The next section of the talk was a look at genetic variation in susceptibility to infectious disease. Dr West explained that there is a genetic factor to susceptibility and susceptibility itself can be divided into two types: susceptibility to catching a disease and susceptibility to dying if the disease is caught. Studies looking at the TLR5 gene have shown that a base change, changing C for T, changes the amino acid to a stop codon and shortens the protein. This means the protein no longer senses flagellin. The T base has been shown to increase someone’s likelihood of getting melioidosis but gives protection if they get the disease.
Dr West then talked about his team’s work with exome sequencing. To reduce the amount of sequencing needed they only looked at extreme phenotypes. These were 45 patients who had only mild melioidosis symptoms and survived the disease, and 42 patients who experienced severe symptoms and died within two days. The sequencing found 13,503 genes with variance. Two of the top five SNPs (single nucleotide polymorphisms) were for lactoferrin.
At this point Dr West gave a little background on lactoferrin. Lactoferrin is a multifunction protein. It has antimicrobial and immunomodulatory properties. There have been mixed results from clinical trials but it has been shown to affect biofilms. Global data seems to show that there has been selection pressure on lactoferrin over time.
Returning to melioidosis Dr West showed how the association of lactoferrin SNPs in melioidosis is driven by females. In fact if only males are looked at, the association disappears. The reason for this difference is not yet explained. Plasma lactoferrin levels have been found to be lower in women with melioidosis. Although it not yet confirmed it is thought lactoferrin may modulate cellular inflammatory responses and bacterial replication.
After a short summary and acknowledgement of his collaborators and funders, Dr West took questions from the audience. The queries were insightful and included ‘Is lactoferrin a cause or effect?’. Dr West explained that currently we don’t know and it may be difficult to find out through only looking at lactoferrin in blood.
Dr West was a thoughtful speaker and his talk, including the interesting Q&A section, was a good learning experience for the researchers and students who attended. Dr West can be considered a ‘global researcher’ and is a long-term Faculty and MORU collaborator. We were delighted to have speak in our lunch talk series and we hope to see him again soon.
Organizer: office of Research Services (ORS) and Department of Microbiology and Immunology (by Assoc. Prof. Narisara Chantratita)
Date & Location: 20 June 2017 at Video Conference Meeting Room, 5th floor, Chalermprakiat Building, Faculty of Tropical Medicine, Mahidol University.
Summary by Ms. Nicola Ball