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nd
               The 2  International Seminar of Science and Technology
               “Accelerating Sustainable innovation towards Society 5.0”
               ISST 2022 FST UT 2022
               Universitas Terbuka
               experience  dormancy  (persister)  which  means  the  bacteria  reduce
               their metabolic activity so that antibiotics become ineffective at killing
               bacteria [16], [25], [27]. According to Stewart [28], usually antibiotics
               works by killing bacteria that metabolically active. Metabolically active
               bacteria have the ability to synthesize macromolecules which are the
               target  molecules  of  antibiotics  in  recognizing  bacteria.  In  contrast,
               inactive or dormant bacteria will not produce macromolecules.
               Another factor that causes biofilm resistance to antibiotics is horizontal
               gene  transfer.  The  high  population  density  in  the  biofilm  allows
               bacteria to carry out symbiosis. The symbiosis that occurs between
               bacteria  causes  gene  transfer.  Bacteria  that  have  plasmids  with
               resistance genes can transfer these genes through a horizontal gene
               transfer  mechanism[11],  [25].  Horizontal  gene  transfer  is  more
               effective in bacteria that live in biofilm compared to planktonic bacteria.
               Krol et al., [29] reported, the gene transfer ability in biofilm is more
               effective 7-700 times. Besides, the structure of the biofilm increases
               the stability of the plasmid and the mobility of the transferred genes.
               The density of bacteria population in the biofilm increases the mobile
               genetic  elements  (MGEs).  The  structure  of  the  biofilm  matrix  also
               maintains the quality of the conjugative pili [30]. This also showed in a
               study  by  Krol  et  al.,  [29]  that  said,  the  gene  transfer  mechanism
               happened if bacteria close with each other which occur if the density
               of the bacterial population is high. Living in biofilm causes bacteria to
               be close to each other, this facilitates the transfer of plasmids [29].
               Based  on  the  explanation  above,  it  can  be  concluded  that  biofilm
               resistance to antibiotics occur due to various factors such as biofilm
               physical  and  physiological  factors,  and  factors  related  to  genetic
               material  [25]. Therefore, biological agent to treat biofilm is needed and
               one that has potential is bacteriophage.

               2.3  Bacteriophage
               Bacteriophage  or  also  called  phage  are  virus  that  infect  bacteria
               (Figure.  3a).  The  name  bacteriophage  comes  from  the  word’s
               bacteria  and  phage  in  which  in  Greek  means  bacteria-eater.  As  a


               ISST 2022 – FST Universitas Terbuka, Indonesia             91
               International Seminar of Science and Technology “Accelerating Sustainable
               Towards Society 5.0
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