hypoactivity protection in candida biofilms

[Guest guest]

ID docs - who I dont think ever(?) take the bowel candida idea

seriously - do treat people for a variety of well accepted pathogenic

fungal infections, which mostly occur in immunodeficiency. My

lecturers in a couple of not-terribly-hefty courses have said that

getting rid of these things is a complete pain, so I think that is

probably at least a rule of thumb. I have meant to examine whether

that difficulty could be due to hypoactivity protection. This new Kim

investigation is consistent with that idea, but I havent read

the full text to see if it strongly implies that idea.

Excerpt:

" Interestingly, surviving C. albicans persisters were only detected

in biofilms, and not in planktonic exponentially growing or

stationary populations. Reinoculation of cells surviving killing of

the biofilm by amphotericin B produced a new biofilm with a new

subpopulation of persisters. This suggests that C. albicans

persisters are not mutants, but phenotypic variants of the wild type. "

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Antimicrob Agents Chemother. 2006 Aug 21; [Epub ahead of print]

Related Articles, Books

Candida albicans Biofilms Produce Antifungal-Tolerant Persister Cells.

Lafleur MD, Kumamoto CA, K.

Department of Biology, Northeastern University, 360 Huntington Ave,

Boston, MA, 02115; Department of Molecular Biology and Microbiology,

Tufts University, 136 on Ave, Boston, MA, 02111.

Fungal pathogens form biofilms that are highly recalcitrant to

antimicrobial therapy. _Expression of multidrug resistance pumps in

young biofilms has been linked to increased resistance to azoles, but

this mechanism does not seem to underlie the resistance of mature

biofilms that are a model of in vivo infection. The mechanism of drug

resistance of mature biofilms remains largely unknown. We report that

biofilms formed by the major human pathogen Candida albicans exhibit

a strikingly biphasic killing pattern in response to two microbicidal

agents, amphotericin B, a polyene antifungal, and chlorhexidine, an

antiseptic, indicating that a subpopulation of highly tolerant cells,

termed persisters, existed. The extent of killing with a combination

of amphotericin B and chlorhexidine was similar to that observed with

individually added antimicrobials. Thus, surviving persisters form a

multidrug tolerant subpopulation. Interestingly, surviving C.

albicans persisters were only detected in biofilms, and not in

planktonic exponentially growing or stationary populations.

Reinoculation of cells surviving killing of the biofilm by

amphotericin B produced a new biofilm with a new subpopulation of

persisters. This suggests that C. albicans persisters are not

mutants, but phenotypic variants of the wild type. Using a stain for

dead cells, rare dark cells were visible in a biofilm after

amphotericin B treatment and a bright and a dim population were

physically sorted from this biofilm. Only the dim cells produced

colonies, showing that this method allows the isolation of yeast

persisters. Given that persisters only formed in biofilms, mutants

defective in biofilm formation were examined for tolerance to

amphotericin B. All of the known mutants affected in biofilm

formation were able to produce normal levels of persisters. This

finding indicates that attachment rather than formation of a complex

biofilm architecture initiates persister formation. Bacteria produce

multidrug tolerant persister cells in both planktonic and biofilm

populations and it appears that yeasts and bacteria have evolved an

analogous strategy that assigns the function of survival to a small

part of the population. In bacteria, persisters are dormant cells. It

remains to be seen whether attachment initiates dormancy which leads

to the formation of fungal persisters. This study suggests that

persisters may be largely responsible for the multidrug tolerance of

fungal biofilms.

PMID: 16923951 [PubMed - as supplied by publisher]