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Gram Variable Bacteria

 

When performing Gram staining, be aware that bacteria may not always exhibit the same gram reaction.   For instance, gram-positive cells that should stain purple, end up staining pink.  And, gram-negative cells that should stain pink, stain purple.  When this occurs, bacteria are said to be gram-variable.  Unfortunately, such erroneous gram reactions could lead to the misidentification of bacteria.  Below are some of the factors that can contribute to these discrepancies:

 

  1. Dirty slides:  Poor Gram stain results might occur if smears are prepared on dirty slides. Oils and other grime on the slide might alter the effectiveness of the reagents.  Slides should always be thoroughly pre-cleaned.

 

  1. Uneven smears:  Cells should always be spread into a thin, single layer of cells.  If a smear exhibits uneven thickness, overlapping cells may not get the proper exposure to the reagents.  This results in uneven or mottled staining.  For example, in the thicker areas of the smear, gram-negative cells may not decolorize sufficiently and end up staining purple. 

 

  1. Overheating smears:  Excessive heat while heat-fixing a smear is a potential problem.  This heat may alter or damage cell wall, thereby making them decolorize more readily.  Under this circumstance, gram-positive cells tend to stain pink.

 

  1. Faulty reagents:  The use of faulty reagents might lead to erroneous gram reactions.  For example, Gram’s iodine loses its effectiveness over time due to exposure to air and higher temperatures.  Insufficient iodine exposure could cause cells to decolorize more readily.  Similarly, cells tend to decolorize too easily if crystal violet is prepared at a concentration that is too low.  In either case, gram-positive cells end up staining pink.  

 

  1. Excessive decolorizing:  When ethyl alcohol is used too abundantly or too long, a smear can be overdecolorized.  As a result, gram-positive cells lose all the crystal violet and end up staining pink.         

 

  1. Excessive rinsing:  Another source of overdecolorization can occur with excessive washing between steps.  Water could remove the crystal violet from gram-positive cells  before the Gram’s iodine is applied, thus causing them to stain pink.                    

 

  1. Excessive counterstaining:  If safranin is applied for a prolonged period, this excessive counterstaining will replace the crystal violet in gram-positive cells and make them stain pink.       

 

  1. Old cultures:  For the most reliable results, it is recommended that cultures used for Gram staining should be 18-24 hours old.  Smears prepared from old cultures tend to stain inconsistently.  The older cells in the smear have damaged cell walls that decolorize more readily, making gram-positive cells stain pink. 

 

  1. Broth cultures:  Smears prepared from broth cultures may lead to more gram-variable reactions.  Because this fluid medium ends up being transferred to slide, the ingredients found in broths are thought to interfere with the staining process.   To avoid this complication, smears can be made from the surface growth of bacteria cultured on solid media. 

 

  1. Non-conforming bacteria:  Because of the unique chemical composition of some bacteria, these organisms simply do not conform to the typical gram reactions observed with most bacteria.  In addition to gram-variable species, some bacteria may simply stain very poorly or not at all.  These bacteria (e.g., Mycobacterium spp.) are then termed Gram neutral.   

 

Bibliography

 

LanaGram™”.  Hardy Diagnostics.  2002.  Nov. 6, 2003  http://www.hardydiagnostics.com/catalog/hugo/LanaGram.htm

 

Kelly, S.G., and F.J. Post.  “Gram Stain.”  Basic Microbiology Techniques (4th ed.) 85-88 (2002).  Star Publishing Company, Belmont, CA.

 

Kruczak-Filipov, P. and R. Shively.  “Gram stain procedure.”  In: Isenberg, H.D. (ed.). Clinical Microbiology Procedures Handbook.  Vol. 1, 1.5.1-1.5.18 (1992).   American Society for Microbiology, Washington, D.C.

 

McClelland, R.  “Gram’s stain: The key to microbiology.”  Medical Laboratory Observer 20-28 (April 2001).  Nov. 6, 2003  http://www.mlo-online.com