Persister cells, dormancy and infectious disease.

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Full text at:

http://www.biology.neu.edu/pdf/KL2007Pers.pdf

Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4. Persister cells, dormancy and infectious disease. K. Antimicrobial Discovery Center, Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. k.lewis@... Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review. Publication Types: * Research Support, N.I.H., Extramural * Review PMID: 17143318 [PubMed - indexed for MEDLINE]

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really good. Please put it in the files/links section. Also, please remind me of others that I've said should be included there, but have forgotten to do. pennyNelly Pointis <janel@...> wrote: Full text at: http://www.biology.neu.edu/pdf/KL2007Pers.pdf Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4. Persister cells, dormancy and infectious disease. K. Antimicrobial Discovery Center, Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. k.lewisneu (DOT) edu Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The

molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review. Publication Types: * Research Support, N.I.H., Extramural * Review PMID: 17143318 [PubMed - indexed for MEDLINE]

[Guest guest]

An interesting quote from that article:

A disarmingly simple approach to sterilize an infec-

tion was first proposed by Bigger in 1944 (REF. 1). The

proposal is to kill bacterial cells with a high dose of an

antibiotic, then allow the antibiotic concentration to

decrease, which will enable persisters to resuscitate and

start to grow. If a second dose of antibiotic is adminis-

tered shortly after persisters start to grow, a complete

sterilization might be achieved. This approach is success-

ful in vitro, and a P. aeruginosa biofilm can essentially

be sterilized with 2 consecutive applications of a fluo-

roquinolone (K. L., unpublished observations). Perhaps

understandably, this approach has not been received with

enthusiasm by specialists in clinical microbiology. The

goal of established therapies is to maintain the plasma

level of an antibiotic at a maximum concentration, in

order to discourage the development of resistance. Most

importantly, an optimal pulse-dosing regimen would

probably vary from patient to patient. However, it seems

that some patients might have inadvertently taken solv-

ing the problem of intractable persistent infections into

their own hands. Individuals who suffer from persistent

infections that require a lengthy therapy are often cured,

but why a year-long regimen is better than a month-long

one is unclear. An efficacious fluctuating dose of antibi-

otics administered serendipitously by the patient might

be responsible for persister eradication in these cases.

The patients might adjust drug dosing simply through

being absent-minded, which sooner or later could pro-

duce the perfect drug-administration regimen. Curing

persistent infections might therefore result from patient

non-compliance. Analysing how persistent infections are

cured might shed light on the likelihood of developing

a rational regimen for the pulse-dosing sterilization of

infection.

On Sat, Mar 24, 2007 at 07:28:43PM +0100, Nelly Pointis wrote:

>Full text at:

>

>http://www.biology.neu.edu/pdf/KL2007Pers.pdf

>

>Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4.

>

>

> Persister cells, dormancy and infectious disease.

>

> K.

>

> Antimicrobial Discovery Center, Department of Biology, Northeastern

>University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.

>k.lewis@...

>

> Several well-recognized puzzles in microbiology have remained unsolved

>for decades. These include latent bacterial infections, unculturable

>microorganisms, persister cells and biofilm multidrug tolerance.

>Accumulating evidence suggests that these seemingly disparate phenomena

>result from the ability of bacteria to enter into a dormant (non-dividing)

>state. The molecular mechanisms that underlie the formation of dormant

>persister cells are now being unravelled and are the focus of this Review.

>

> Publication Types:

>

> * Research Support, N.I.H., Extramural

> * Review

>

>

> PMID: 17143318 [PubMed - indexed for MEDLINE]

[Guest guest]

Definitely interesting. I can relate, both about taking matters into my own hands, and also sometimes lapsing. I've been taking abx for so long that it sometimes doesn't seem to matter if I'm too tired to take my pills before bed. Especially when I'm feeling good. Or once in a while, I just feel I need a break from the pills for a day or two, like I just can't take another pill. After a day or two of that, I can feel the infection starting to come back, which gets me off my butt and back on the meds. I've been steadily improving so perhaps this guy's onto something, and just by chance my lapses have been my body telling me to do exactly what he's describing? Right now, my energy level's the best it's been in a couple of years at least. What I'm not sure how to deal with is the inflammation. I've still got one hip and one shoulder that are seriously messed up (my other shoulder, which was frozen, is fine now,

even though doc said I'd need surgery on it). My hips, legs and ankles are incredibly stiff. It's like a reactive arthritis and I'm not sure what to do about it. I don't believe I just suddenly developed all over arthritis. I believe it's an inflammatory reaction that may be self sustaining at this point. pennyNorman Yarvin <norman.yarvin@...> wrote: An interesting quote from that article:A disarmingly simple approach to sterilize an infec-tion was first proposed

by Bigger in 1944 (REF. 1). Theproposal is to kill bacterial cells with a high dose of anantibiotic, then allow the antibiotic concentration todecrease, which will enable persisters to resuscitate andstart to grow. If a second dose of antibiotic is adminis-tered shortly after persisters start to grow, a completesterilization might be achieved. This approach is success-ful in vitro, and a P. aeruginosa biofilm can essentiallybe sterilized with 2 consecutive applications of a fluo-roquinolone (K. L., unpublished observations). Perhapsunderstandably, this approach has not been received withenthusiasm by specialists in clinical microbiology. Thegoal of established therapies is to maintain the plasmalevel of an antibiotic at a maximum concentration, inorder to discourage the development of resistance. Mostimportantly, an optimal pulse-dosing regimen wouldprobably vary from patient to patient. However, it

seemsthat some patients might have inadvertently taken solv-ing the problem of intractable persistent infections intotheir own hands. Individuals who suffer from persistentinfections that require a lengthy therapy are often cured,but why a year-long regimen is better than a month-longone is unclear. An efficacious fluctuating dose of antibi-otics administered serendipitously by the patient mightbe responsible for persister eradication in these cases.The patients might adjust drug dosing simply throughbeing absent-minded, which sooner or later could pro-duce the perfect drug-administration regimen. Curingpersistent infections might therefore result from patientnon-compliance. Analysing how persistent infections arecured might shed light on the likelihood of developinga rational regimen for the pulse-dosing sterilization ofinfection.On Sat, Mar 24, 2007 at 07:28:43PM +0100, Nelly Pointis

wrote:>Full text at:>>http://www.biology.neu.edu/pdf/KL2007Pers.pdf>>Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4.>>> Persister cells, dormancy and infectious disease.>> K.>> Antimicrobial Discovery Center, Department of Biology, Northeastern >University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. >k.lewisneu (DOT) edu>> Several well-recognized puzzles in microbiology have remained unsolved >for decades. These include latent bacterial infections, unculturable >microorganisms, persister cells and biofilm multidrug tolerance. >Accumulating evidence suggests that these seemingly disparate phenomena >result from the ability of bacteria to enter into a dormant (non-dividing) >state. The

molecular mechanisms that underlie the formation of dormant >persister cells are now being unravelled and are the focus of this Review.>> Publication Types:>> * Research Support, N.I.H., Extramural> * Review>>> PMID: 17143318 [PubMed - indexed for MEDLINE]