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Atypical bacteria are bacteria that do not color with gram-staining but rather remain colorless: they are neither Gram-positive nor Gram-negative. These include the Chlamydiaceae, Legionella and the Mycoplasmataceae ; the Rickettsiaceae are also often considered atypical. Spirochetes are also considered atypical bacteria.
Gram-positive bacteria have a thick peptidoglycan layer in their cell wall, which retains the crystal violet during Gram staining, resulting in a purple color. Gram-negative bacteria have a thin peptidoglycan layer which does not retain the crystal violet, so when safranin is added during the process, they stain red.
The Mycoplasmataceae lack a peptidoglycan layer so do not retain crystal violet or safranin, resulting in no color. The Chlamydiaceae contain an extremely thin peptidoglycan layer, preventing visible staining. Ricketsiaceae are technically Gram-negative, but are too small to stain well, so are often considered atypical.
Peptidoglycans are the site of action of beta-lactam antibiotics such as penicillins and cephalosporins, so mycoplasma are naturally resistant to these drugs, which in this sense also makes them “atypical” in the treatment of their infections. Macrolides such as erythromycin however, are usually effective in treating atypical bacterial infections.