Bacterial DNA content measurement using flow cytometry

From: Arvind Natarajan (nataraja@biosci.cbs.umn.edu)
Date: Thu May 06 1999 - 10:03:33 EST


In our experience, it is possible to stain and quantitate bacterial DNA
content using propidium iodide after ethanol fixation and RNAase
treatment.  Durodie et al. (pp 95-110, Flow cytometry in Microbiology,
David Lloyd ed., Springer-Verlag, 1993) have published a protocol for
measuring ploidy of E.coli cells.  We have optimized a protocol for DNA
staining of Gram positive streptococcal species (J. Micro. Meth.
34(3):223-233, 1999).  The critical steps appear to be lysozyme and
mutanolysin treatment after ethanol fixation, and using DNAase-free RNAase
A for removing ds RNA prior to PI staining (we use the protocol from
Sambrook et al., Volume III, 2nd. edition, 1989, for making our RNAaseA
DNAase-free). Using our protocol, we were able to discern peaks in DNA
distributions of streptococci growing in chains that corresponded to
integral multiples of chromosome equivalents.   As always, controls (such
as antibiotic-treated cells containing an integral number of chromosomes)
are essential for correct interpretation of data.

In an aside, we have noticed that ethanol fixation significantly reduces
green fluorescence intensity from Gfp in S.cerevisiae cells (J.
Biotechnol. 62(1):29-45, 1998), although we have not done a similar study
in bacterial cells.

Arvind Natarajan
University of Minnesota

_______________________________________________________________________________
Howard Shapiro writes:

Unfortunately, if you want to measure DNA accurately in bacteria, you will
almost certainly have to find a machine with either UV or blue-violet (436
to 457 nm) excitation, because only DAPI and the Hoechst dyes (UV-excited)
and the mithramycin-ethidium combination (blue-violet excited) appear to
provide adequate DNA specificity. Other dyes (and ethidium when used alone)
stain double-stranded RNA as well as DNA; while RNAse treatment removes 
the interference from RNA in mammalian cells, it has, as far as I know,
not been possible to permeabilize bacterial cells sufficiently to allow
RNAse digestion of the RNA while preserving the DNA.  While
7-aminoactinomycinD is excitable at 488 nm and DNA-specific, it does not
give good stoichiometric staining and has a low quantum efficiency,
eliminating it from consideration thus far for quantitative work on
bacteria.  There are several machines in the Harvard medical area which
could provide UV or blue-violet excitation; staining protocols appear in
an article by Steen et al in Volume 42 of Methods in Cell Biology.

_______________________________________________________________________________
Arne Rietsch writes:

>I'd like to use FACS to analyze the DNA content of bacterial cells in a
>population (the question is if the bacterium we're studying segregates
>daughter cells carrying only one of the chromosomes under starvation
>conditions. These cells should be detectable as a population with
>dramatically reduced DNA content.)
>I was wondering if there are protocolls out there for staining bacteria
>for FACS analysis. Preferably a stain that does not overlap with the
>emisssion spectrum of GFP. Also the FACS that is available to me does not
>have a UV laser, i.e. DAPI will not work.



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