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ACCIONES JURÍDICAS

2. Principales repertorios de acción colectiva utilizados por La Mesa y CDD

was  purified  (EZNA  Cycle-­‐Pure  kit,  Omega  Bio-­‐tek)  and  mixed  with  0.2  µl  10x  PCR  

Thermo  buffer,  0.2  µl  Taq  polymerase  (5.0  U  µl-­‐1),  0.4  µl  10  mM  dATPs  for  a  final  

concentration  of  0.2  mM,  to  a  final  volume  of  20  µl.  The  reaction  was  incubated  for  

15  minutes  at  72°C  and  the  product  subsequently  ligated  with  pCR8  following  the  

standard  protocol  as  follows  (Invitrogen):  4  µl  of  the  PCR  product  was  incubated  

with  1  µl  salt  solution  and  1  µl  TOPO  vector  for  5  minutes  at  room  temperature  

and  then  placed  on  ice.  Two  µl  of  the  TOPO  ligation  mixture  was  added  to  a  vial  of   thawed   One-­‐shotTM   chemically   competent   cells   and   incubated   on   ice   for   25  

minutes.  After  exposing  the  cells  to  a  heat  shock  for  30  sec  at  42°C,  250  µl  of  SOC  

medium   was   added.   After   one   hour   incubation   at   37°C,   25  µl,   50  µl   and   75  µl  

aliquots   of   bacterial   culture   were   spread   on   LB-­‐agar   plates   containing   spectinomycin,  and  incubated  overnight  at  37°C.  Colonies  were  selected  from  the  

plate   the   following   day   and   sent   for   sequencing   to   confirm   that   the  carB*   insert   was   introduced   into   the   plasmid   without   any   additional   mutations.   The   strains   were  stored  at  -­‐80°C.  

   

2.4.3 Cloning  into  the  pUIC3  plasmid    

E.coli  carrying   pCR8-­‐carB*   was   grown   in   5   ml   LB   overnight   in   the   presence   of   spectinomycin.   After   purification   (EZNA   Plasmid   mini   kit,   Omega   Bio-­‐tek)   the   plasmid  was  digested  with  Bgl  II.  In  a  total  volume  of  50  µl,  1  µg  of  vector  DNA  was  

mixed   with   5  µl   10x   NEB   3   buffer,   1  µl  Bgl  II   enzyme   (10   U  µl-­‐1)   and   H2O   and  

incubated  for  1-­‐2  hours  at  37°C.  The  fragment  was  separated  from  the  vector  by  

gel  electrophoresis  in  a  1%  TAE  agarose  gel  at  a  voltage  of  100,  cut  out  of  the  gel   and  purified.  The  product  was  stored  at  -­‐20°C  until  ligation  with  plasmid  pUIC3.  

The   suicide   reporter   plasmid   pUIC3   contains   a   tetracycline   resistance   gene,   a   promoter  less  lacZY  operon  and  a  multiple  cloning  site  (Rainey,  1999).  The  vector   is   relatively   large   and   as   a   consequence   a   higher   volume   of   cell   culture   must   be   mixed   with   the   plasmid   to   obtain   a   sufficient   yield   of   transformants.   Therefore,  

two  5  ml  LB  overnight  cultures  were  inoculated  with  E.colipUIC3  and  incubated  at   37°C  overnight.  After  plasmid  purification  2  µg  of  plasmid  DNA  was  linearised  by  

digestion   with   2  µl  Bgl  II   (10   U  µl-­‐1),   10  µl   10x   NEB   3   buffer,   and   H20   to   a   final  

volume  of  100  µl.  The  linearised  vector  was  isolated  by  gel  electrophoresis  in  a  1%  

TAE  gel  and  purified.  To  prevent  self-­‐ligation  the  digested  vector  was  treated  with   Antarctic   phosphatase   to   remove   5’-­‐phosphate   groups   from   the   ends:   1  µg   of  

linearised  vector  DNA  was  mixed  with  0.5  units  of  CIP  and  incubated  at  37°C  for  

one  hour.  The  product  was  cleaned  with  a  PCR  clean  up  kit  (EZNA  Cycle-­‐Pure  kit,   Omega  Bio-­‐tek)  and  stored  at  -­‐20°C.  

Before  ligating  the  carB  fragment  with  pUIC3  the  concentration  of  both  insert  and   vector   were   estimated   by   spectrometry   (BioPhotometer,   Eppendorf).   The   ligase   reaction   contained   a   molar   ratio   of   3:1   of   insert   to   vector:   1.45  µl   of   linearised  

pUIC3  was  added  to  7.05  µl  of  the  carB  fragment,  1.0  µl  10x  NEB  buffer,  and  0.5  µl  

ligase,  and  incubated  at  16°C  overnight.  DNA  ligase  was  inactivated  by  heating  the  

reaction  to  65°C  for  20  minutes,  and  stored  at  4°C  until  transformation  into  E.  coli.  

   

2.4.3.1 Manufacture  of  electrocompetent  cells  

 

Electrocompetent  E.coliDH5αλpir  were  prepared  by  the  method  of  Sambrook  and   Russell  (Sambrook  &  Russell,  2001).  The  starter  culture,  5  ml  LB,  was  inoculated   from  the  freezer  stock  and  grown  overnight  at  37°C.  3  ml  of  the  starter  culture  was  

used  to  inoculate  a  flask  with  350  ml  LB  that  was  pre-­‐heated  to  37°C.  The  OD600  of  

the   culture   was   monitored   every   15-­‐20   minutes.   When   OD600   reached   between  

~0.35-­‐0.4,  the  flask  was  transferred  to  ice  for  20  minutes  to  stop  further  growth.   Then,  the  culture  was  decanted  into  six  x  50  ml  chilled  centrifuge  tubes.  The  cells   were  pelleted  at  4°C,  at  900  x  g  for  15  minutes.  The  supernatant  was  discarded  and  

the  cells  were  washed  with  50  ml  chilled  H2O.  The  cells  were  pelleted  at  4°C,  at  900  

x  g  for  15  minutes  and  the  supernatant  was  discarded.  The  second  wash  followed   the   same   procedure.   In   the   final   wash   the   pellets   were   resuspended   in   50   ml   of   chilled  10%  glycerol,  pooled  in  one  tube  that  was  centrifuged  at  4°C,  at  900  x  g  for  

15  minutes,  and  the  supernatant  was  discarded.  The  pellet  was  resuspended  in  the   residual   liquid   and   aliquots   of   50   µL   were   transferred   into   pre-­‐chilled  

microcentrifuge  tubes  and  stored  at  -­‐80°C.  

   

2.4.3.2 Transformation  of  pUIC3  into  E.  coli  

 

An   aliquot   of   E.coliDH5αλpir   electrocompetent   cells   was   thawed   on   ice   and   subsequently   mixed   with   2.5  µl   of   the   pUIC3carB*-­‐construct.   The   mixture   was  

pipetted  into  a  pre-­‐chilled  2  mm  cuvette  that  was  inserted  into  an  Elecroporator   (Electroporator   2510;   Eppendorf).   The   voltage   was   set   at   2.5   KV   and   after   electroporation   500  µl   SOC   were   immediately   added   to   the   cell   suspension.   The  

culture   recovered   for   one   hour   at   37°C   and   was   then   plated   on   LB   agar   plates  

containing  Ampicillin  and  X-­‐gal.  The  next  day  several  blue  colonies  were  selected   from   the   plate   and   a   PCR   was   performed   using   vector   specific   primers.   Colonies   that   showed   a   correctly-­‐sized   insert   were   inoculated   into   LB   broth,   grown   overnight  at  37°C,  and  stored  at  -­‐80°C.  

   

2.4.4 Bacterial  conjugation    

The  carB*  mutation  was  introduced  into  P.  fluorescens  through  tri-­‐parental  mating.   Conjugative   plasmid   transmission   from   the   donor   strain  E.colipUIC3carB*   to   a  P.   fluorescens  recipient   strain   was   assisted   by   the   Km   resistant   helper   plasmid  

pRK2013,  which  provided  mob  and  tra  functions  in  trans  (Ditta  et  al.,  1980).  The   donor   and   the   helper   were   grown   overnight   in   5   ml   LB   with   the   appropriate   antibiotics,  and  the  recipient  without  any  antibiotics.  The  next  day  the  OD600  was  

measured   to   ensure   equal   amounts   of   each   culture   to   optimise   pUIC3carB*   transmission   frequency.   Approximately   700  µl   of   the   recipient   was   subjected   to  

heat   shock   conditions   at   45°C   for   20   minutes.   300  µl   of   the   donor   and   helper