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MICROBIAL ATP

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     SUMMARY:  ATP, an obligate constituent of all living 
     organisms, is extracted from viable microorganisms in 
     boiling TRIS buffer following sample concentration by 
     vacuum filtration.  The extracted ATP is analyzed in a 
     photometer by the firefly bioluminescence reaction, and     
     the ATP content is related to total living (biomass) 
     microbial carbon by the application of a laboratory-
     derived extrapolation factor. 
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1.  Principle

    In field studies it is often desirable to determine the total 
amount of living cellular material (biomass).  Conventional methods 
(i.e., fresh or dry weight determinations, rate of increase of cell 
numbers, etc.) usually cannot be used owing to (a) lack of sensitivity 
in the analytical procedures, (b) the presence of a heterogeneous 
assemblage of organisms, (c) the presence of dead cells and (d) the 
presence of detrital (non-living) organic material which is not 
associated with the living cells.  Estimation of cellular biomass 
by measurement of adenosine triphosphate (ATP) is not limited by any 
of these considerations.

    The rationale for using ATP to estimate biomass is the ubiquitous 
distribution of ATP in all living cells, the rapid loss of ATP from 
dead cells and the fairly uniform concentration of ATP in the protoplasm 
of all microbial cells.  Data on ATP concentrations can thus be 
extrapolated to biomass parameters, such as cellular organic carbon 
or dry or fresh weight (Holm-Hansen, 1973).  ATP is extracted from 
cells using boiling TRIS buffer and is stored frozen (-20 °C) prior 
to analysis by firefly bioluminescence.


2.  Precautions

    ATP samples must be processed as rapidly as possible, because the 
ATP content of microorganisms can change rapidly when cells are stressed.  
Furthermore, a phenomenon referred to as the "filtration effect" causes 
a loss of ATP when cells are exposed to dessicating conditions 
immediately after the water is drawn through the filter pad (Karl 
and Holm-Hansen, 1978).  For this reason it is very important that 
the samples are filtered immediately upon sampling and extracted 
immediately upon filtration; any delay will cause a decline in ATP 
content.  Because the firefly bioluminescence assay is inhibited by 
metals, it is also important to use clean stainless steel forceps when 
handling the filters.  It is also essential that the extraction buffer 
(TRIS) is boiling (100 °C), as inefficient extraction results at 
temperatures (<95 °C).  TRIS buffer boiling must be confirmed before 
starting the filtration process.


3.  Sampling, Filtration, Extraction and Storage

3.1. Samples for ATP determinations are collected in clean Niskin 
     bottles attached to the rosette/CTD unit.

3.2. As soon as the samples arrive on deck, water is prefiltered 
     through a drawing tube containing an in-line 202 µm Nitex mesh 
     prefilter to remove large zooplankton and particles which might 
     otherwise affect the precision and accuracy of microbial biomass 
     determinations.  Samples are drawn into 4-liter polyethylene 
     bottles that are rinsed 3 times with approximately 100-200 ml 
     seawater from the appropriate depth.  Filtration is begun 
     immediately (be sure heating block is on and has achieved a 
     temperature >110 °C; time required ~1 hour).  

3.3. Filter triplicate samples at each depth through 47 mm GF/F filters.  
     Total volume required per sample will depend on depth:  between 
     0-150 m use 1 liter per sample, below 150 m use 2 liters per sample.

3.4. As soon as the last few drops of water have passed through the 
     filter, remove the filter tower from the base, fold the filter 
     in half then in half again and plunge the folded filter into 5 
     ml of boiling TRIS buffer (pH 7.4; 0.02 M) which is kept partially 
     covered to eliminate evaporative volume loss.  Try to avoid 
     "bumping" of the TRIS buffer (caused by superheating of the 
     buffer).  

3.5. After a 5 minute extraction period, remove the tubes from the heating 
     block, allow to cool to approximately room temperature, secure the 
     rubber stoppers and freeze (-20 °C) in upright position.

3.6. In order to minimize sample cross-contamination it is best to start 
     with deepest sample, which, in most cases, contains the lowest 
     concentration of ATP.


4.  Analysis

4.1. Prepare enough firefly lantern extract (Sigma Chemical Co., FLE-50) 
     to process all samples and at least ten external ATP reference 
     standards.  Lyophilized FLE-50 should be reconstituted in 5 ml 
     distilled water and allowed to "age" at room temperature for at 
     least 6 hours (but no longer than 24 hours) in order to reduce 
     the background luminescence.  Approximately 1 hour before 
     starting the assay, dilute each 50 mg vial of reconstituted 
     FLE-50 with 15 ml of sodium arsenate buffer (0.1 M, pH 7.4) 
     and 15 ml of MgSO4  (0.04 M).  Immediately before use, filter 
     the FLE-50 mixture through a GF/F filter.

4.2. Turn on ATP photometer at least 30 minutes before use.

4.3. Prepare set of ATP reference standards ranging from 0.1-100 ng 
     ATP ml-1 (see Chapter 16, section 5). 

4.4. Using the automatic injector and computer-assisted photometer, 
     analyze the peak height of light emission (0-15 seconds) for 
     each sample and standard.


5.  Preparation of ATP Standards

    A primary (reference) ATP standard is prepared by dissolving 
exactly 10 mg of high purity (99.9%) ATP (sodium salt) into exactly 
10 ml of sterile distilled water.  Be sure to weigh out an amount 
equivalent to 10 mg of free acid form of ATP (not 10 mg of hydrated 
Na-ATP) taking into account the cation contribution and average 
hydration state of the molecule.  This latter information is supplied 
by the manufacturer.  Immediately prepare 1/10 and 1/100 dilutions 
of the primary stock, place a portion of each solution into a 1 cm 
quartz spectrophotometercuvette and measure the absorbance at 259 nm.  
Calculate the exact concentration as follows:

                              A = Elc

where:  A = absorption at 259 nm
        E = ATP molar extinction coefficient (15.4 x 103)
        l = path length (cm)
        c = concentration of ATP in moles per liter

    After calculating the precise concentration of ATP in the primary 
standard, dilute the stock (gravimetrically) into sterile-filtered 
(0.2 µm) 0.02 M TRIS buffer pH 7.4 to yield an ATP standard solution 
of exactly 1 µg ml-1.  Compare with "old" standard and if different 
by >|1%|, repeat the dilution step.  Store frozen in 1 ml aliquots.

    Working standards, ranging from 0.1-100 ng ATP ml-1, are prepared 
by diluting a vial of the primary standard with freshly-prepared TRIS 
buffer (0.02 M) just prior to use.  These working standards are 
discarded at the end of the day.


6.  Data Reduction and Calculations

6.1. Plot ATP standard data and calculate linear regression statistics 
     for the standard curve.  Use LOTUS spreadsheet to calculate ATP 
     concentration (ng l-1) from data on peak height (relative to 
     standards), volume of extract and volume of sample filtered.

6.2. ATP concentrations can be related to total biomass by applying 
     the extrapolation factor; 250 x ATP = C (Karl, 1980).  This 
     relationship is based upon direct laboratory and field analyses 
     performed over the past two decades.  While there is a range 
     in the C/ATP ratio for microorganisms grown under a variety 
     of environmental conditions, the relationship of C/ATP = 250 
     appears to be reasonable for samples collected from the 
     oligotrophic North Pacific Ocean (Laws et al., 1987).


7.  Equipment/Supplies

    Niskin bottles and rosette
    sample bottles and tygon tubing
    heating block and test tubes
    ATP photometer (Biospherical Instrument Co.)
    stainless forceps
    glass fiber filters (Whatman; 47 mm GF/F)


8.  Reagents

    TRIS buffer (0.02 M, pH 7.4)
    magnesium sulfate (0.04 M)
    sodium arsenate buffer (0.1 M; pH 7.4)
    firefly lantern extract (FLE-50; Sigma Chemical Co.)
    reagent ATP (Sigma Chemical Co.)


9.  References

    Holm-Hansen, O.  1973.  Determination of total microbial biomass 
    by measurement of adenosine triphosphate.  In: Estuarine Microbial 
    Ecology, L. H. Stevenson and R. R. Colwell, editors, University 
    of South Carolina Press, Columbia, pp. 73-89.

    Karl, D. M.  1980.  Cellular nucleotide measurements and 
    applications in microbial ecology.  Microbiological Reviews, 44, 
    739-796.

    Karl, D. M. and O. Holm-Hansen.  1978.  Methodology and measurement 
    of adenylate energy charge ratios in environmental samples. 
    Marine Biology, 48, 185-197.

    Laws, E. A., D. G. Redalje, L. W. Haas, P. K. Bienfang, R. W. 
    Eppley, W. G. Harrison, D. M. Karl and J. Marra.  1984.  High 
    phytoplankton growth and production rates in oligotrophic 
    Hawaiian coastal waters. Limnology and Oceanography, 29, 1161-1169.