Cell wall deficient forms of mycobacteria: a review

Abstract

Cell wall deficient (CWD)-forms or L-forms of bacteria are characterized by a complete or partial loss of cell wall components and by the change of cellular shape. CWD-forms (spheroplasts) of bacteria are commonly prepared in vitro and are used for various practical applications. However, very little is known about the conditions required for the formation of CWD-forms of bacteria and mycobacteria in vivo and their significance in aetiology of various chronic diseases of humans (tuberculosis, sarcoidosis, and Crohn's disease) and animals (paratuberculosis). It is quite difficult to detect CWD-forms of mycobacteria in biological material and the possibilities of their detection by microscopy, culture, DNA hybridization techniques and other methods are limited. This obviously leads to a relatively small amount of published data on the detection and the isolation of CWD-forms of mycobacteria both from human or veterinary biological material, which can lead to the conclusion of a non-infectious origin of the diseases. The present review also includes studies performed by authors from the former Soviet Union and likely represents the first complete summarization of their knowledge in this sphere. However, certain results may be viewed as somewhat controversial. Accordingly, more attention should be paid to the research of cell wall deficient forms, not only in association with chronic and latent mycobacterial infections.Keywords: protoplasts; antituberculotics; reversion; intestine; respiratory tract; basilar tuberculosis; skin tuberculosis; lymph node; Johne's disease, Mycobacterium tuberculosis complex; Mycobacterium avium complex; zoonoses; food safety List of abbreviations: AFR = acid-fast rods; AG = arabinogalactan; AT = antituberculotics; BCG = Bacillus Calmette-Guerin; CFU = colony forming units; CWD-forms = cell wall deficient forms; DNA = deoxyribonucleic acid; E = ethambutol; ELISA = enzyme-linked immunosorbent assay; EM = electron microscopy; GPL = glycopeptidolipids; H = isoniazid; HEYM = Herrold's egg yolk medium; HPC = hexadecylpyridinium chloride (N-cetylpyridinium chloride monohydrate); LAM = lipoarabinomannan; LOS = extractable glycolipids; M. = Mycobacterium; MIC = minimum inhibition concentration; M7H9 = Middlebrook 7H9; PAS = para-amino-salycilic acid; PCR = polymerase chain reaction; PGL = phenolic glycolipids; pv. = pseudovar; R = rifampicin; RFLP = restriction fragment lenght polymorphism; SDS PAGE = sodium dodecyl sulphate polyacrylamide gel electrophoresis; S = streptomycin; TSB = tryptic soy broth; Z = pyrazinamide; ZN = Ziehl-Neelsen

Cell Wall Deficiency in Mycobacteria: Latency and Persistence

“…A variety of papers reported about production of mycobacterial L-forms experimentally in vitro, using different inducing factors. Wide range of substances (cell wall inhibitors) as antibiotics, lytic enzymes and some amino acids affecting cell wall and especially biosynthesis of peptidoglycan have been used as L-inducing factors (Beran et al, 2006;Hammes et al, 1973;Hines and Styer, 2003;Naser et al, 1993;Udou et al, 1983). Indeed, it is important to understand how mycobacteria regulate the cell wall composition in response to changing environment.…”

“…However, a lot of papers, reviews (Allan et al, 2009;Beran et al, 2006;Domingue and Woody, 1997;Domingue, 2010;Gumpert & Taubeneck, 1983;Onwuamaegbu et al, 2005;Zhang, 2004) and several monographs (Domingue, 1982;Mattman, 2001;Prozorovski et al, 1981), support the concept that L-forms can be induced in vivo, can persist there for a significant span of time and can be the cause for latent, chronic and relapsing/recurrent infections, as well as for diseases of unknown infectious-allergic or autoimmune origin.…”

Crohn's disease and related inflammatory diseases: from many single hypotheses to one "superhypothesis"

“…Some characteristics are common to all of them, while some are specific and surprising. Some mycobacteria can sometimes change according to the environment (Bull et al 2013;Rosu et al 2013), others can alter their cell wall and/or can form cell wall-deficient forms or spheroroplasts by losing the cell wall, or can form resistant cells similar to spores (Hines and Styer 2003;Beran et al 2006).…”

Genetic and morphologic variations during L-form conversion in Mycobacterium tuberculosis

“…The ability of M. tuberculosis to survive and reproduce as L-forms is assumed as one of the adaptive reactions of mycobacteria towards unfavourable factors-absence of nutrients, pH of the medium, damaging physical and chemical factors, inhibitors of cell wall biosynthesis such as antibiotics and host immune factors such as lysozyme, compliment, antibodies, etc. (Beran et al, 2006;Mattman, 2001;Markova, 2012).…”