Biofilms, DNA Transformation, Drug Resistance
How Gut Bacteria Exchange DNA and Resist Antibiotics
Oct 12, 2009
One of the classic experiments of molecular biology is Frederick Griffith’s discovery of genetic transformation, the transfer of genes (DNA) from one bacterium to another. Transfer of genes is a health problem, because it means that genes for resistance to antibiotics can quickly move from feedlot to emergency room.
Triggered Release of DNA
Early experiments showed that DNA was released from bacteria. Other bacteria then picked up the DNA and either digested it or used recombination systems to incorporate the foreign DNA into their own chromosomes. It was initially thought that bacteria released their DNA as a result of death and lysis. It is now known that bacteria in biofilms release copies of their DNA in response to community signals, quorum sensing.
Biofilm Bacteria Communicate by Quorum Sensing
Bacteria grow, divide and form clumps of cells, microcolonies. The metabolism of each cell modifies its surroundings and bacteria respond to their presence in a microcolony through the release and uptake of autoinducers, such as various homoserine lactones. The advantage of this adaptation, quorum sensing, is that it permits bacteria to adjust their metabolisms as either an isolated, planktonic hermit, or in the midst of a bacterial community, such as a group of bioluminescent bacteria or a gut biofilm.
Secreted DNA as Matrix or Gene Exchange
There are advantages to bacteria that extrude copies of their DNA chromosome into the external environment:
- Genes that code for DNA exchange mechanisms have very high selective advantage, i.e. the genes quickly spread through a population of bacteria.
- DNA accumulating around bacteria in a colony will provide a defensive barrier. Antimicrobial peptides are positively charged and DNA is negatively charged.
- DNA can be used to hold bacterial communities together and to adhere to host cells.
Uptake of External DNA May Be Risk or Benefit
Bacteria have specific mechanisms to take up DNA, i.e. to make them competent at transformation. The proteins that provide competence are expressed as a response to a biofilm community and quorum sensing. Thus, bacteria in a biofilm release DNA into the biofilm and other bacteria take up some of that DNA. Bacteria use a host restriction system to evaluate incoming DNA and degrade virus or otherwise dangerous DNA. DNA from related bacteria is recombined into the host chromosome. Incorporation of foreign DNA provides another source of genetic diversity in the biofilm community.
Bacteria in Biofilms Are Protected from Antibiotics
Antibiotics have traditionally been obtained from fungi, and are small molecules that disrupt critical bacterial functions such as DNA replication, protein synthesis or cell wall assembly. Bacteria can also produce enzymes that inactivate antibiotics. Bacterial genes for antibiotic resistance can be readily transferred in biofilms between different bacterial species. In fact the genetic promiscuity of gut bacteria corrupts the typical definitions of species. Gut biofilms permit the construction of bacterial species to exploit available nutritional sources. The layered structure of biofilm communities provides enough of a barrier so that biofilm bacteria can resist up to 100 times the antibiotic concentration that would normal kill them. Acidic polysaccharides and DNA of the biofilm matrix also provide protection from basic antimicrobial peptides that are host defenses.
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