Views
3 years ago

Annual Review 2011 - Wellcome Trust

Annual Review 2011 - Wellcome Trust

Combating infectious

Combating infectious diseaseRace against resistance: as fast as we developnew antibiotics and vaccines, bacteria developresistance to them.Understanding the precise geneticevents that enable the evolution ofdrug resistance in bacteria could helpus design more powerful – andpermanent – ways of controllinginfection.In a paper published in the journalScience in January 2011, WellcomeTrust-funded researchers described indetail the adaptive changes that allowa drug-resistant form of Streptococcuspneumoniae, called PMEN1, tocontinue to thrive.The team at the Wellcome TrustSanger Institute and Imperial CollegeLondon used next-generationDNA-sequencing technology toanalyse 240 samples of PMEN1collected over 24 years. Theycompared the DNA sequences,looking for differences over that time.The findings revealed for the firsttime the patterns of genomicadaptation that have allowed thePMEN1 strain to fight its evolutionarywar against our vaccines andantibiotics in recent decades. Theyshowed that S. pneumoniae evolvesand reinvents itself with remarkablespeed: the degree of diversity betweenbacteria within the PMEN1 strainitself was surprising.The critical first step in unlocking theevolutionary history of the PMEN1lineage was separating two kinds ofDNA change. Vertical changes occurwhen bacterial cells divide to createoffspring, while horizontal changesare when pieces of DNA are swappedbetween two bacteria.Mapping the vertical changes – DNAmutations passed down throughdirect ancestry – enabled theresearchers to construct anevolutionary tree. They saw that thedrug-resistant PMEN1 lineageoriginated around 1970 – about thetime that the widespread use ofantibiotics was introduced to fightpneumococcal disease.They could then see that thehorizontal transfer of DNA betweenbacteria had affected three-quartersof the S. pneumoniae genome.Hotspots particularly prone tohorizontal transmission often codedgenes for antigens – molecules thattrigger an immune response inhumans – suggesting thatS. pneumoniae evades vaccines andantibiotics by changing the antigensthat are being targeted.The authors also identifieddifferences in the patterns ofadaptation in response to antibioticsand vaccines. With antibiotics,different strains often adapted in thesame way to become resistant. In thecase of vaccines, however, there was adecline in the prevalence of bacteriasusceptible to the vaccine, whichopened the door for others that couldevade the vaccine to fill the niche andbecome dominant.Further focused sequencingprogrammes may prove crucial to thefuture fight against this and otherbacterial pathogens that use similarmechanisms to outsmart our controlmeasures.Streptococcus pneumoniae bacteria.Steve Gschmeissner/SPLAnnual Review 2011 | 29

Annual Review 2004 - Wellcome Trust
Wellcome Trust Annual Review 2009
Annual Review 2000 - Wellcome Trust
Wellcome Library: The Year in Review 2009 - Wellcome Trust
Women and Peer Review - Wellcome Trust
TRUST FINANCE PLC ANNUAL REPORT AND ... - Wellcome Trust
Science and the Public A Review of Science ... - Wellcome Trust
Wellcome Trust Annual Report and Financial Statements 2009
Wellcome Trust Finance plc Annual Report and Financial ...
Review of Wellcome Trust PhD Training: The student perspective
Portfolio Review. Malaria 1990-2009 - Wellcome Trust
Review and Prospectus 2002 - Wellcome Trust Centre For Cell ...
Review and Prospectus 2006 - Wellcome Trust Centre For Cell ...
Informal Science Learning Review: Reflections ... - Wellcome Trust
Annual Report and Financial Statements 2007 - Wellcome Trust
Annual Report and Financial Statements 2003 - Wellcome Trust
Summarised Annual Report And Financial ... - Wellcome Trust
Wellcome Trust Annual Report and Financial Statements 2008
2011 Annual Review - The Dartington Hall Trust
Wellcome News 68 - Wellcome Trust
Wellcome History 43 - Wellcome Trust
Review of Research Using Non-Human Primates - Wellcome Trust
Wel1come Trust - Wellcome Trust
Assessment Framework Report vol. 1, 2011/12 - Wellcome Trust
Annual Review 2011/12 - Severn Gorge Countryside Trust
Annual Review - The Disabilities Trust