Cell Wall–Deficient Bacterial Infections

Overview of Cell Wall–Deficient Bacterial Infections

First Described: 1935, London (Kleineberger)¹

Causes: Cell wall–deficient strains of a variety of gram-positive and gram-negative bacteria

Major Clinical Signs: Chronic draining or ulcerated soft tissue and skin lesions, polyarthritis, possibly other chronic pyogenic and pyogranulomatous lesions

Differential Diagnoses: Infections due to other fastidious bacteria such as Mycoplasma, Nocardia, Mycobacterium, Bartonella, Brucella, nutritionally variant streptococci such as Granulicatella, or, for animals with polyarthritis, Borrelia burgdorferi; fungal infections (e.g., due to Sporothrix schenckii or Coccidioides immitis); persistence of a foreign body; neoplasia; congenital immunodeficiency; primary immune-mediated disease

Human Health Significance: Likely similar to that for the corresponding walled (or “normal”) variant of the bacterial species involved

Etiologic Agent and Epidemiology

Cell wall–deficient bacteria (CWDB), also known as L-phase or L-form bacteria, are bacterial variants that lack a cell wall, although they may in fact possess small amounts of peptidoglycan.² The name L-form was given to these bacteria because they were discovered at the Lister Institute in London. L-form bacteria are distinct from mycoplasmas, because Mycoplasma spp. do not originate from bacteria that normally possess a cell wall. A huge variety of gram-positive and gram-negative bacterial species may become CWDB when exposed to certain stressors in the laboratory (such as antimicrobial drugs) (Box 39-1). Some of these bacteria remain as CWDB (stable L-forms), whereas others revert back to possession of a cell wall (unstable L-forms). CWDB assume a spherical or pleomorphic shape, and are susceptible to osmotic lysis. However, they resist β-lactam drugs such as penicillin, and may be able to evade the innate immune response. Thus, it has been proposed that reversion to cell wall–deficient forms may be a mechanism of bacterial persistence. Although the formation of CWDB has been well documented in the laboratory, the role that CWDB play in disease remains controversial.³

BOX 39-1 Examples of Medically Important Bacteria That May Become Cell Wall–Deficient When Subjected to Appropriate Stressors