BIOL 142 Chapter Notes - Chapter 22.4: Mycobacterium Tuberculosis, Rpob, Missense Mutation
30 Apr 2018
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22.4$Evolution$in$Action:$Recent$Research$on$Natural$
Selection$
!!
Case%Study%1:%How%did%Mycobacterium-tuberculosis%become%resistant%to%
antibiotics?!
Tuberculosis!
• Mycobacterium-tuberculosis!is!the!bacteria!that!causes!tuberculosis%(TB):!a!disease!of!the!lungs!
caused!by!infection!with!the!bacterium!Mycobacterium-tuberculosis!
o Infects!the!lungs,!causes!fever,!coughing,!sweats,!weight!loss,!and!often!death!
• It!receded!in!importance!during!the!early!1900s!because!of:!
o Advances!in!nutrition!made!people!better!able!to!fight!off!most!M.-tuberculosis!infections!
quickly!
o The!development!of!antibiotics!allowed!physicians!to!stop!infections!
• In!the!late!1980s,!rates!of!tuberculosis!surged!because!strains!responsible!for!the!increase!were!
largely!or!completely!resistant!to!antibiotics!that!were!once!effective!
!!
A!patient!history!
• Man!was!admitted!to!hospital!,!10!months!after!treatment!for!TB,!bacterial!cultures!from!the!
patient's!chest!fluid!indicated!no!M.-tuberculosis!cells!and!had!normal!X-rays!
o Antibiotics!seemed!to!clear!the!infection!
• 2!months!after!the!TB!tests!proved!normal,!he!was!readmitted!
• He!was!treated!with!a!variety!of!antibiotics,!including!rifampin,!and!died!of!respiratory!failure!10!
days!later!
• Samples!of!fluid!from!his!lungs!showed!that!M.-tuberculosis!was!growing!actively,!but!were!
resistant!to!rifampin!
• Difference!was!a!point!mutation!in!the!rpoB!gene!in!C!-->!T!
!!
A!mutation!in!a!bacterial!gene!confers!resistance!
• The!rpoB!gene!codes!for!a!component!of!RNA!polymerase!that!transcribes!DNA!to!mRNA!
o Essential!for!the!survival!and!reproduction!of!bacterial!cells!
o The!missense!mutation!caused!a!change!in!the!amino!acid!sequence!of!te!RNA!polymerase!
and!changed!its!shape!
• Rifampin!worked!by!binding!to!the!RNA!polymerase!of!M.-tuberculosis!and!interfering!with!
transcription!
• These!results!suggest!the!steps!that!led!to!this!patient's!death…!
o Completely!by!chance,!one!or!a!few!of!the!bacterial!cells!present!in!the!patient!before!the!
onset!of!drug!therapy!happened!to!have!the!rpoB!allele!with!the!C-->T!mutation!
• Under!normal!conditions,!mutant!forms!of!RNA!polymerase!do!not!work!as!well!as!the!
more!common!form!
§ Cells!with!this!mutation!would!not!proudce!as!many!offspring!and!would!stay!at!
low!frequency,!even!while!the!overall!population!grew!to!the!point!of!inducing!
symptoms!that!sent!the!young!man!to!the!hospital!
o Therapy!with!rifampin!began!
• In!response,!cells!in!the!population!with!normal!RNA!polymerase!began!to!slow!much!
more!slowly!or!died!
Document Summary
22. 4 evolution in action: recent research on natural. Tuberculosis: mycobacterium tuberculosis is the bacteria that causes tuberculosis (tb): a disease of the lungs caused by infection with the bacterium mycobacterium tuberculosis. Infects the lungs, causes fever, coughing, sweats, weight loss, and often death. It receded in importance during the early 1900s because of: advances in nutrition made people better able to fight off most m. tuberculosis infections quickly, the development of antibiotics allowed physicians to stop infections. In the late 1980s, rates of tuberculosis surged because strains responsible for the increase were largely or completely resistant to antibiotics that were once effective. Samples of fluid from his lungs showed that m. tuberculosis was growing actively, but were resistant to rifampin: difference was a point mutation in the rpob gene in c --> t. A mutation in a bacterial gene confers resistance.
