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Malini Basu
Pine Crest School
• 2013: 23,000 deaths due to chronic bacterial
infections
• Number of hospital visits due to reoccurring
bacterial infections has doubled in the last 5 years
• Bacterial infections are a global health concern
because of increasing mortality rates
• Bacterial colonies including persister cells are often
found in biofilms
• Biofilms are often naturally occurring on indwelling
medical devices such as catheters and valve
replacements
• What are persister cells?
• Microbial cells
• Dormant in the presence of antibiotics
• Multidrug tolerancy
• Comparison to sensitive cells
• Genetically identical
• Rarity: 1 persister in 1 million normal (sensitive) cells
• Persisters rare occurrence makes it hard to perform
research on them
• Often found in biofilms
Insisting on Persisting
Insisting on Persisting
http://jmm.sgmjournals.org/content/60/6/699/F2.expansion
• Persister Cells
• Function: Survival
• Can be created from oxidative stress
• Most common bacteria with persisters
• E coli. and Staphylococcus
• Aminoglycosides
• Only current treatment for E coli
• Key difference between resistant cells
and persisters
• Persister Cells go into a state of dormancy in
the presence of antibiotics
• Antibiotics function via the inhibition of
important cellular functions such as translation
while the cell is growing
• No growth = no affect of antibiotics
DORMANT
PERSISTER
• Amino-modified glycoside (sugar)
• Exhibits protein synthesis inhibiting qualities
• Has been proven effective in E Coli Persister
Cell eradication
• hipA gene (High Persistence A)
• Regulates the function of hipA proteins which can
prevent cells from growing
• Mutations in hipA gene have shown increased
production of Persisters
• hipB proteins bind to hipA and function as a
regulator
• Lack of hipB leads to free hipA proteins which lead
to a greater production of Persisters
• Incurable airway infections in CF patients
have been linked to Persister Cells
• A study in CF patients revealed hipA and
hipB mutations in bacterial cells of CF
infections
• Other kinds of treatment options
• Biofilms on medial devices are located on commonly
used prosthetic limbs and other implants
• What allows persisters to act in the way they
do
• Regardless of being genetically identical to sensitive
cells
• http://www.nature.com/emi/journal/v3/n1/full/emi20143a.html
• http://www.nytimes.com/2013/09/17/health/cdc-report-finds-23000-deaths-a-year-from-antibiotic-resistant-infections.html?_r=0
• Kenn, G. Et al. 2013 Antibiotics: Killing the survivor. Nature, 503, 347-349
• Klein, E. Et al. 2007 Hospitalizations and Deaths Caused by methicillin-Resistant Staphylococcus aureus, United States, 1999-2005 Emerging
Infectious Diseases, Volume 13, (Number 12)
• Lewis, K. 2010 “Persister Cells and the Paradox of Chronic Infections” [On-Line],
https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic-
infections&catid=664&Itemid=882
• https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic-
infections&catid=664&Itemid=882
• http://jb.asm.org/content/192/23/6191.full
• Persister cells and tolerance to antimicrobials Iris Keren, Niilo Kaldalu, Amy Spoering, Yipeng Wang, Kim Lewis Department of Biology,
Northeastern University, 360 Huntington Avenue, Mugar 405, Boston, MA 02115, USA Received 29August 2003; received in revised form 31
October 2003; accepted 1 November 2003 First published online 28 November 2003
• http://www.nature.com/nrmicro/journal/v5/n1/abs/nrmicro1557.html
• http://www.nature.com/nrmicro/journal/v5/n1/full/nrmicro1557.html
• https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic-
infections&catid=664&Itemid=882
• http://www.readcube.com/articles/10.1038/nrmicro1557

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Insisting on Persisting

  • 2. • 2013: 23,000 deaths due to chronic bacterial infections • Number of hospital visits due to reoccurring bacterial infections has doubled in the last 5 years
  • 3. • Bacterial infections are a global health concern because of increasing mortality rates • Bacterial colonies including persister cells are often found in biofilms • Biofilms are often naturally occurring on indwelling medical devices such as catheters and valve replacements
  • 4. • What are persister cells? • Microbial cells • Dormant in the presence of antibiotics • Multidrug tolerancy • Comparison to sensitive cells • Genetically identical • Rarity: 1 persister in 1 million normal (sensitive) cells • Persisters rare occurrence makes it hard to perform research on them • Often found in biofilms
  • 8. • Persister Cells • Function: Survival • Can be created from oxidative stress • Most common bacteria with persisters • E coli. and Staphylococcus • Aminoglycosides • Only current treatment for E coli • Key difference between resistant cells and persisters
  • 9. • Persister Cells go into a state of dormancy in the presence of antibiotics • Antibiotics function via the inhibition of important cellular functions such as translation while the cell is growing • No growth = no affect of antibiotics
  • 11. • Amino-modified glycoside (sugar) • Exhibits protein synthesis inhibiting qualities • Has been proven effective in E Coli Persister Cell eradication
  • 12. • hipA gene (High Persistence A) • Regulates the function of hipA proteins which can prevent cells from growing • Mutations in hipA gene have shown increased production of Persisters • hipB proteins bind to hipA and function as a regulator • Lack of hipB leads to free hipA proteins which lead to a greater production of Persisters
  • 13. • Incurable airway infections in CF patients have been linked to Persister Cells • A study in CF patients revealed hipA and hipB mutations in bacterial cells of CF infections
  • 14. • Other kinds of treatment options • Biofilms on medial devices are located on commonly used prosthetic limbs and other implants • What allows persisters to act in the way they do • Regardless of being genetically identical to sensitive cells
  • 15. • http://www.nature.com/emi/journal/v3/n1/full/emi20143a.html • http://www.nytimes.com/2013/09/17/health/cdc-report-finds-23000-deaths-a-year-from-antibiotic-resistant-infections.html?_r=0 • Kenn, G. Et al. 2013 Antibiotics: Killing the survivor. Nature, 503, 347-349 • Klein, E. Et al. 2007 Hospitalizations and Deaths Caused by methicillin-Resistant Staphylococcus aureus, United States, 1999-2005 Emerging Infectious Diseases, Volume 13, (Number 12) • Lewis, K. 2010 “Persister Cells and the Paradox of Chronic Infections” [On-Line], https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic- infections&catid=664&Itemid=882 • https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic- infections&catid=664&Itemid=882 • http://jb.asm.org/content/192/23/6191.full • Persister cells and tolerance to antimicrobials Iris Keren, Niilo Kaldalu, Amy Spoering, Yipeng Wang, Kim Lewis Department of Biology, Northeastern University, 360 Huntington Avenue, Mugar 405, Boston, MA 02115, USA Received 29August 2003; received in revised form 31 October 2003; accepted 1 November 2003 First published online 28 November 2003 • http://www.nature.com/nrmicro/journal/v5/n1/abs/nrmicro1557.html • http://www.nature.com/nrmicro/journal/v5/n1/full/nrmicro1557.html • https://www.microbemagazine.org/index.php?option=com_content&view=article&id=2848:persister-cells-and-the-paradox-of-chronic- infections&catid=664&Itemid=882 • http://www.readcube.com/articles/10.1038/nrmicro1557