1887

Abstract

Historically, many species of bacteria have been reported to produce viable, cell wall deficient (CWD) variants. A variety of terms have been used to refer to CWD bacteria and a plethora of methods described in which to induce, cultivate and propagate them. In this review, we will examine the long history of scientific research on CWD bacteria examining the methods by which CWD bacteria are generated; the requirements for survival in a CWD state; the replicative processes within a CWD state; and the reversion of CWD bacteria into a walled state, or lack thereof. In doing so, we will present evidence that not all CWD variants are alike and that, at least in some cases, CWD variants arise through an adaptive lifestyle switch that enables them to live and thrive without a cell wall, often to avoid antimicrobial activity. Finally, the implications of CWD bacteria in recurring infections, tolerance to antibiotic therapy and antimicrobial resistance will be examined to illustrate the importance of greater understanding of the CWD bacteria in human health and disease.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-08-04
2024-12-05
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References

  1. Young KD. The selective value of bacterial shape. Microbiol Mol Biol Rev 2006; 70:660–703 [View Article]
    [Google Scholar]
  2. Typas A, Banzhaf M, Gross CA, Vollmer W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 2011; 10:123–136 [View Article]
    [Google Scholar]
  3. Vollmer W, Blanot D, de Pedro MA. Peptidoglycan structure and architecture. FEMS Microbiol Rev 2008; 32:149–167 [View Article] [PubMed]
    [Google Scholar]
  4. Auer GK, Weibel DB. Bacterial cell mechanics. Biochemistry 2017; 56:3710–3724 [View Article]
    [Google Scholar]
  5. Rojas ER, Billings G, Odermatt PD, Auer GK, Zhu L et al. The outer membrane is an essential load-bearing element in gram-negative bacteria. Nature 2018; 559:617–621 [View Article]
    [Google Scholar]
  6. Domingue GJ, Woody HB. Bacterial persistence and expression of disease. Clin Microbiol Rev 1997; 10:320–344 [View Article] [PubMed]
    [Google Scholar]
  7. Dienes L, Weinberger HJ. The L forms of bacteria. Bacteriol Rev 1951; 15:245–288 [View Article]
    [Google Scholar]
  8. Tabor CW. Stabilization of protoplasts and spheroplasts by spermine and other polyamines. J Bacteriol 1962; 83:1101–1111 [View Article] [PubMed]
    [Google Scholar]
  9. Van Rensburg AJ. Properties of Proteus mirabilis and providence spheroplasts. J Gen Microbiol 1969; 56:257–264 [View Article]
    [Google Scholar]
  10. Schuhardt VT, Klesius PH. Osmotic fragility and viability of lysostaphin-induced staphylococcal spheroplasts. J Bacteriol 1968; 96:734–737 [View Article] [PubMed]
    [Google Scholar]
  11. Perty M. Zur kenntnis kleinster Lebensformen nach Bau, Funktionen, Systemtik mit Spezialverzeichniss der in der Schweiz beobachteten. Mittheilungen der Naturforschenden Gesellschaft in Bern 1852231–232
    [Google Scholar]
  12. Klieneberger E. The natural occurrence of pleuropneumonia-like organism in apparent symbiosis with Streptobacillus moniliformis and other bacteria. J Pathol 1935; 40:93–105 [View Article]
    [Google Scholar]
  13. Dienes L. Organisms of Klieneberger and Streptobacillus moniliformis. J Infect Dis 1939; 65:24–42 [View Article]
    [Google Scholar]
  14. Zou J, Kou S-H, Xie R, VanNieuwenhze MS, Qu J et al. Non-walled spherical Acinetobacter baumannii is an important type of persister upon β-lactam antibiotic treatment. Emerg Microbes Infect 2020; 9:1149–1159 [View Article] [PubMed]
    [Google Scholar]
  15. Bernabeu-Wittel M, García-Curiel A, Pichardo C, Pachón-Ibáñez ME, Jiménez-Mejías ME et al. Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii. Clin Microbiol Infect 2004; 10:931–934 [View Article] [PubMed]
    [Google Scholar]
  16. Hanberger H, Nilsson LE, Nilsson M, Maller R. Post-antibiotic effect of beta-lactam antibiotics on gram-negative bacteria in relation to morphology, initial killing and MIC. Eur J Clin Microbiol Infect Dis 1991; 10:927–934 [View Article] [PubMed]
    [Google Scholar]
  17. Gebicki JM, James AM. The preparation and properties of spheroplasts of Aerobacter aerogenes. J Gen Microbiol 1960; 23:9–18 [View Article]
    [Google Scholar]
  18. Horii T, Kobayashi M, Sato K, Ichiyama S, Ohta M. An in-vitro study of carbapenem-induced morphological changes and endotoxin release in clinical isolates of gram-negative bacilli. J Antimicrob Chemother 1998; 41:435–442 [View Article] [PubMed]
    [Google Scholar]
  19. Chikada T, Kanai T, Hayashi M, Kasai T, Oshima T et al. Direct observation of conversion from walled cells to wall-deficient L-form and vice versa in Escherichia coli indicates the essentiality of the outer membrane for proliferation of L-form cells. Front Microbiol 2021; 12:645965 [View Article] [PubMed]
    [Google Scholar]
  20. Glover WA, Yang Y, Zhang Y. Insights into the molecular basis of L-form formation and survival in Escherichia coli. PLoS One 2009; 4:e7316 [View Article] [PubMed]
    [Google Scholar]
  21. Sun Y, Sun T-L, Huang HW. Physical properties of Escherichia coli spheroplast membranes. Biophys J 2014; 107:2082–2090 [View Article]
    [Google Scholar]
  22. Liu I, Liu M, Shergill K. The effect of spheroplast formation on the transformation efficiency in Escherichia coli DH5α. J Exp Microbiol Immunol 2006; 9:81–85
    [Google Scholar]
  23. Joseleau-Petit D, Liébart J-C, Ayala JA, D’Ari R. Unstable Escherichia coli L forms revisited: growth requires peptidoglycan synthesis. J Bacteriol 2007; 189:6512–6520 [View Article] [PubMed]
    [Google Scholar]
  24. Mercier R, Kawai Y, Errington J. General principles for the formation and proliferation of a wall-free (L-form) state in bacteria. Elife 2014; 3:e04629 [View Article]
    [Google Scholar]
  25. Nakao M, Nishi T, Tsuchiya K. In vitro and in vivo morphological response of Klebsiella pneumoniae to cefotiam and cefazolin. Antimicrob Agents Chemother 1981; 19:901–910 [View Article]
    [Google Scholar]
  26. Cross T, Ransegnola B, Shin J-H, Weaver A, Fauntleroy K et al. Spheroplast-mediated carbapenem tolerance in Gram-negative pathogens. Antimicrob Agents Chemother 2019; 63:e00756-19 [View Article]
    [Google Scholar]
  27. Xu Y, Zhang B, Wang L, Jing T, Chen J et al. Unusual features and molecular pathways of Staphylococcus aureus L-form bacteria. Microb Pathog 2020; 140:103970 [View Article] [PubMed]
    [Google Scholar]
  28. Ratnam S, Chandrasekhar S. The pathogenicity of spheroplasts of Mycobacterium tuberculosis. Am Rev Respir Dis 1976; 114:549–554 [View Article] [PubMed]
    [Google Scholar]
  29. Monahan LG, Turnbull L, Osvath SR, Birch D, Charles IG et al. Rapid conversion of Pseudomonas aeruginosa to a spherical cell morphotype facilitates tolerance to carbapenems and penicillins but increases susceptibility to antimicrobial peptides. Antimicrob Agents Chemother 2014; 58:1956–1962 [View Article] [PubMed]
    [Google Scholar]
  30. Watanakunakorn C, Hamburger M. Induction of spheroplasts of Pseudomonas aeruginosa by carbenicillin. Appl Microbiol 1969; 17:935–937 [View Article] [PubMed]
    [Google Scholar]
  31. Yang C, Li H, Zhang T, Chu Y, Zuo J et al. Study on antibiotic susceptibility of Salmonella typhimurium L forms to the third and forth generation cephalosporins. Sci Rep 2020; 10:3042 [View Article] [PubMed]
    [Google Scholar]
  32. Michailova L, Kussovsky V, Radoucheva T, Jordanova M, Markova N. Persistence of Staphylococcus aureus L-form during experimental lung infection in rats. FEMS Microbiol Lett 2007; 268:88–97 [View Article] [PubMed]
    [Google Scholar]
  33. Weaver AI, Murphy SG, Umans BD, Tallavajhala S, Onyekwere I et al. Genetic determinants of penicillin tolerance in Vibrio cholerae. Antimicrob Agents Chemother 2018; 62:e01326-18 [View Article]
    [Google Scholar]
  34. Dörr T, Davis BM, Waldor MK. Endopeptidase-mediated beta lactam tolerance. PLoS Pathog 2015; 11:e1004850 [View Article] [PubMed]
    [Google Scholar]
  35. Allan EJ, Hoischen C, Gumpert J. Bacterial L-forms. Adv Appl Microbiol 2009; 68:1–39 [View Article] [PubMed]
    [Google Scholar]
  36. Rogers MJ, Simmons J, Walker RT, Weisburg WG, Woese CR et al. Construction of the mycoplasma evolutionary tree from 5S rRNA sequence data. Proc Natl Acad Sci USA 1985; 82:1160–1164 [View Article]
    [Google Scholar]
  37. Chen L-L, Chung W-C, Lin C-P, Kuo C-H. Comparative analysis of gene content evolution in phytoplasmas and mycoplasmas. PLoS One 2012; 7:e34407 [View Article] [PubMed]
    [Google Scholar]
  38. Errington J, Mickiewicz K, Kawai Y, Wu LJ. L-form bacteria, chronic diseases and the origins of life. Philos Trans R Soc Lond B Biol Sci 2016; 371:20150494 [View Article] [PubMed]
    [Google Scholar]
  39. Casadesús J. Bacterial L-forms require peptidoglycan synthesis for cell division. Bioessays 2007; 29:1189–1191 [View Article] [PubMed]
    [Google Scholar]
  40. Cross T, Ransegnola B, Shin J-H, Weaver A, Fauntleroy K et al. Spheroplast-mediated carbapenem tolerance in gram-negative pathogens. Antimicrob Agents Chemother 2019; 63:e00756-19 [View Article] [PubMed]
    [Google Scholar]
  41. Billings G, Ouzounov N, Ursell T, Desmarais SM, Shaevitz J et al. De novo morphogenesis in L-forms via geometric control of cell growth. Mol Microbiol 2014; 93:883–896 [View Article] [PubMed]
    [Google Scholar]
  42. Shin J-H, Choe D, Ransegnola B, Hong H-R, Onyekwere I et al. A multifaceted cellular damage repair and prevention pathway promotes high-level tolerance to β-lactam antibiotics. EMBO Rep 2021; 22:e51790 [View Article] [PubMed]
    [Google Scholar]
  43. Panos C, Barkulis SS, Streptococcal L forms I. Effect of osmotic change on viability. J Bacteriol 1959; 78:247–252
    [Google Scholar]
  44. Weibull C. The isolation of protoplasts from Bacillus megaterium by controlled treatment with lysozyme. J Bacteriol 1953; 66:688–695 [View Article]
    [Google Scholar]
  45. Lederberg J. Bacterial protoplasts induced by penicillin. Proc Natl Acad Sci USA 1956; 42:574–577 [View Article]
    [Google Scholar]
  46. de Pedro MA, Donachie WD, Höltje JV, Schwarz H. Constitutive septal murein synthesis in Escherichia coli with impaired activity of the morphogenetic proteins RodA and penicillin-binding protein 2. J Bacteriol 2001; 183:4115–4126 [View Article] [PubMed]
    [Google Scholar]
  47. May JR, Roberts DE, Ingold A, Want SV. Osmotically stable L forms of Haemophilus influenzae and their significance in testing sensitivity to penicillins. J Clin Pathol 1974; 27:560–564 [View Article] [PubMed]
    [Google Scholar]
  48. Want SV, May JR. Induction of L-forms of Haemophilus influenzae in vitro. J Med Microbiol 1975; 8:369–373 [View Article] [PubMed]
    [Google Scholar]
  49. Fuller E, Elmer C, Nattress F, Ellis R, Horne G et al. Beta-lactam resistance in Staphylococcus aureus cells that do not require a cell wall for integrity. Antimicrob Agents Chemother 2005; 49:5075–5080 [View Article] [PubMed]
    [Google Scholar]
  50. Mickiewicz KM, Kawai Y, Drage L, Gomes MC, Davison F et al. Possible role of L-form switching in recurrent urinary tract infection. Nat Commun 2019; 10:4379 [View Article] [PubMed]
    [Google Scholar]
  51. Osawa M, Erickson HP. L form bacteria growth in low-osmolality medium. Microbiology 2019; 165:842–851 [View Article]
    [Google Scholar]
  52. King JR, Gooder H. Induction of enterococcal L-forms by the action of lysozyme. J Bacteriol 1970; 103:686–691 [View Article]
    [Google Scholar]
  53. Kawai Y, Mickiewicz K, Errington J. Lysozyme counteracts β-lactam antibiotics by promoting the emergence of L-form bacteria. Cell 2018; 172:1038–1049 [View Article]
    [Google Scholar]
  54. Rosu V, Bandino E, Cossu A. Unraveling the transcriptional regulatory networks associated to mycobacterial cell wall defective form induction by glycine and lysozyme treatment. Microbiol Res 2013; 168:153–164 [View Article]
    [Google Scholar]
  55. Markova N, Slavchev G, Michailova L, Jourdanova M. Survival of Escherichia coli under lethal heat stress by L-form conversion. Int J Biol Sci 2010; 6:303–315 [View Article]
    [Google Scholar]
  56. Slavchev G, Michailova L, Markova N. Stress-induced L-forms of Mycobacterium bovis: a challenge to survivability. New Microbiol 2013; 36:157–166 [PubMed]
    [Google Scholar]
  57. Espinosa E, Daniel S, Hernández SB, Goudin A, Cava F et al. L-Arabinose induces the formation of viable non-proliferating spheroplasts in Vibrio cholerae. Appl Environ Microbiol 2020; 87:e02305-20 [View Article]
    [Google Scholar]
  58. Ramijan K, Ultee E, Willemse J, Zhang Z, Wondergem JAJ et al. Stress-induced formation of cell wall-deficient cells in filamentous actinomycetes. Nat Commun 2018; 9:5164 [View Article] [PubMed]
    [Google Scholar]
  59. Mearls EB, Izquierdo JA, Lynd LR. Formation and characterization of non-growth states in Clostridium thermocellum: spores and L-forms. BMC Microbiol 2012; 12:180 [View Article] [PubMed]
    [Google Scholar]
  60. McIntosh D, Austin B. Recovery of cell wall deficient forms (L-forms) of the fish pathogens Aeromonas salmonicida and Yersinia ruckeri. Syst Appl Microbiol 1990; 13:378–381 [View Article]
    [Google Scholar]
  61. Dienes L, Weinberger HJ, Madoff S. The transformation of typhoid bacilli into L forms under various conditions. J Bacteriol 1950; 59:755–764 [View Article]
    [Google Scholar]
  62. Ongenae V, Mabrouk AS, Crooijmans M, Rozen D, Briegel A et al. Reversible bacteriophage resistance by shedding the bacterial cell wall. Open Biol 2021; 12:210379
    [Google Scholar]
  63. Dulaney EL, Marx LM. A folic acid linked system in bacterial cell wall synthesis?. J Antibiot 1971; 24:713–714 [View Article]
    [Google Scholar]
  64. Domínguez-Cuevas P, Mercier R, Leaver M, Kawai Y, Errington J. The rod to L-form transition of Bacillus subtilis is limited by a requirement for the protoplast to escape from the cell wall sacculus. Mol Microbiol 2012; 83:52–66 [View Article] [PubMed]
    [Google Scholar]
  65. Leaver M, Domínguez-Cuevas P, Coxhead JM, Daniel RA, Errington J. Life without a wall or division machine in Bacillus subtilis. Nature 2009; 457:849–853 [View Article]
    [Google Scholar]
  66. Mueller EA, Levin PA. Bacterial cell wall quality control during environmental tress. mBio 2020; 11:e02456-20 [View Article] [PubMed]
    [Google Scholar]
  67. Kumar S, Mollo A, Kahne D, Ruiz N. The bacterial cell wall: from lipid II flipping to polymerization. Chem Rev 2022; 122:8884–8910 [View Article]
    [Google Scholar]
  68. Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P. The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev 2008; 32:234–258 [View Article] [PubMed]
    [Google Scholar]
  69. Macheboeuf P, Contreras-Martel C, Job V, Dideberg O, Dessen A. Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev 2006; 30:673–691 [View Article] [PubMed]
    [Google Scholar]
  70. Lederberg J, St Clair J. Protoplasts and L-type growth of Escherichia coli. J Bacteriol 1958; 75:143–160 [View Article]
    [Google Scholar]
  71. Chang TW, Weinstein L. Morphological changes in gram-negative bacilli exposed to cephalothin. J Bacteriol 1964; 88:1790–1797 [View Article]
    [Google Scholar]
  72. Pandey N, Cascella M. Beta Lactam Antibiotics Treasure Island, FL: StatPearls Publishing; 2022
    [Google Scholar]
  73. Jackson JJ, Kropp H. Differences in mode of action of β-lactam antibiotics influence morphology, LPS release and in vivo antibiotic efficacy. J Endotoxin Res 2016; 3:201–218 [View Article]
    [Google Scholar]
  74. Curtis NA, Orr D, Ross GW, Boulton MG. Affinities of penicillins and cephalosporins for the penicillin-binding proteins of Escherichia coli K-12 and their antibacterial activity. Antimicrob Agents Chemother 1979; 16:533–539 [View Article] [PubMed]
    [Google Scholar]
  75. Spratt BG. Properties of the penicillin-binding proteins of Escherichia coli K12. Eur J Biochem 1977; 72:341–352 [View Article] [PubMed]
    [Google Scholar]
  76. Spratt BG. Distinct penicillin binding proteins involved in the division, elongation, and shape of Escherichia coli K12. Proc Natl Acad Sci USA 1975; 72:2999–3003 [View Article]
    [Google Scholar]
  77. Curtis NA, Orr D, Ross GW, Boulton MG. Competition of beta-lactam antibiotics for the penicillin-binding proteins of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli: comparison with antibacterial activity and effects upon bacterial morphology. Antimicrob Agents Chemother 1979; 16:325–328 [View Article] [PubMed]
    [Google Scholar]
  78. Sumita Y, Fukasawa M, Okuda T. Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin-binding proteins and morphological changes. J Antibiot 1990; 43:314–320 [View Article]
    [Google Scholar]
  79. Onoda T, Enokizono J, Kaya H, Oshima A, Freestone P et al. Effects of calcium and calcium chelators on growth and morphology of Escherichia coli L-form NC-7. J Bacteriol 2000; 182:1419–1422 [View Article] [PubMed]
    [Google Scholar]
  80. Laubacher ME, Ades SE. The Rcs phosphorelay is a cell envelope stress response activated by peptidoglycan stress and contributes to intrinsic antibiotic resistance. J Bacteriol 2008; 190:2065–2074 [View Article] [PubMed]
    [Google Scholar]
  81. Silver LL. Fosfomycin: mechanism and resistance. Cold Spring Harb Perspect Med 2017; 7:a025262 [View Article]
    [Google Scholar]
  82. Rodicio MR, Manzanal MB, Hardisson C. Protoplast-like structures formation from two species of Enterobacteriaceae by fosfomycin treatment. Arch Microbiol 1978; 118:219–221 [View Article] [PubMed]
    [Google Scholar]
  83. Schmid EN. Fosfomycin-induced protoplasts and L-forms of Staphylococcus aureus. Chemotherapy 1984; 30:35–39 [View Article] [PubMed]
    [Google Scholar]
  84. Schmid EN. Unstable L-form of Proteus mirabilis induced by fosfomycin. Chemotherapy 1985; 31:286–291 [View Article] [PubMed]
    [Google Scholar]
  85. Isono F, Katayama T, Inukai M, Haneishi T. Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. III. Biological properties. J Antibiot 1989; 42:674–679 [View Article]
    [Google Scholar]
  86. Isono F, Inukai M, Takahashi S, Haneishi T, Kinoshita T et al. Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. II. Structural elucidation. J Antibiot 1989; 42:667–673 [View Article]
    [Google Scholar]
  87. Isono F, Inukai M. Mureidomycin A, a new inhibitor of bacterial peptidoglycan synthesis. Antimicrob Agents Chemother 1991; 35:234–236 [View Article]
    [Google Scholar]
  88. Zhu X, Liu D, Singh AK, Drolia R, Bai X et al. Tunicamycin mediated inhibition of wall teichoic acid affects Staphylococcus aureus and Listeria monocytogenes cell morphology, biofilm formation and virulence. Front Microbiol 2018; 9:1352 [View Article]
    [Google Scholar]
  89. Michel MF, Hijmans W. The additive effect of glycine and other amino acids on the induction of the L-phase of group A -haemolytic streptococci by penicillin and D-cycloserine. J Gen Microbiol 1960; 23:35–46 [View Article]
    [Google Scholar]
  90. Dienes L, Zamecnik PC. Transformation of bacteria into L forms by amino acids. J Bacteriol 1952; 64:770–771 [View Article]
    [Google Scholar]
  91. Watanakunakorn C. Cycloserine induction, propagation, and antimicrobial susceptibility of wall-defective Staphylococcus aureus. Infect Immun 1971; 3:438–443 [View Article] [PubMed]
    [Google Scholar]
  92. Azam MA, Jayaram U. Inhibitors of alanine racemase enzyme: a review. J Enzyme Inhib Med Chem 2016; 31:517–526 [View Article] [PubMed]
    [Google Scholar]
  93. Hammes W, Schleifer KH, Kandler O. Mode of action of glycine on the biosynthesis of peptidoglycan. J Bacteriol 1973; 116:1029–1053 [View Article] [PubMed]
    [Google Scholar]
  94. Nickerson WJ, Webb M. Effect of folic acid analogues on growth and cell division of nonexacting microorganisms. J Bacteriol 1956; 71:129–139 [View Article]
    [Google Scholar]
  95. Bermingham A, Derrick JP. The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery. Bioessays 2002; 24:637–648 [View Article] [PubMed]
    [Google Scholar]
  96. AlRabiah H, Allwood JW, Correa E, Xu Y, Goodacre R. pH plays a role in the mode of action of trimethoprim on Escherichia coli. PLoS One 2018; 13:e0200272 [View Article] [PubMed]
    [Google Scholar]
  97. Klainer AS, Russell RR. Effect of the inhibition of protein synthesis on the Escherichia coli cell envelope. Antimicrob Agents Chemother 1974; 6:216–224 [View Article] [PubMed]
    [Google Scholar]
  98. Klainer AS, Perkins RL. Surface manifestations of antibiotic-induced alterations in protein synthesis in bacterial cells. Antimicrob Agents Chemother 1972; 1:164–170 [View Article] [PubMed]
    [Google Scholar]
  99. Waisbren SJ, Hurley DJ, Waisbren BA. Morphological expressions of antibiotic synergism against Pseudomonas aeruginosa as observed by scanning electron microscopy. Antimicrob Agents Chemother 1980; 18:969–975 [View Article] [PubMed]
    [Google Scholar]
  100. Salton MR. The properties of lysozyme and its action on microorganisms. Bacteriol Rev 1957; 21:82–100 [View Article]
    [Google Scholar]
  101. Salton MR, Ghuysen JM. The structure of di- and tetrasaccharides released from cell walls by lysozyme and Streptomyces F 1 enzyme and the beta(1 to 4) N-acetylhexos-aminidase activity of these enzymes. Biochim Biophys Acta 1959; 36:552–554 [View Article]
    [Google Scholar]
  102. Birdsell DC, Cota-Robles EH. Production and ultrastructure of lysozyme and ethylenediaminetetraacetate-lysozyme spheroplasts of Escherichia coli. J Bacteriol 1967; 93:427–437 [View Article] [PubMed]
    [Google Scholar]
  103. Marvin HJ, Witholt B. A highly efficient procedure for the quantitative formation of intact and viable lysozyme spheroplasts from Escherichia coli. Anal Biochem 1987; 164:320–330 [View Article] [PubMed]
    [Google Scholar]
  104. Ellison RT, Giehl TJ. Killing of gram-negative bacteria by lactoferrin and lysozyme. J Clin Invest 1991; 88:1080–1091 [View Article] [PubMed]
    [Google Scholar]
  105. Ranjit DK, Young KD. The Rcs stress response and accessory envelope proteins are required for de novo generation of cell shape in Escherichia coli. J Bacteriol 2013; 195:2452–2462 [View Article] [PubMed]
    [Google Scholar]
  106. Dell’Era S, Buchrieser C, Couvé E, Schnell B, Briers Y et al. Listeria monocytogenes L-forms respond to cell wall deficiency by modifying gene expression and the mode of division. Mol Microbiol 2009; 73:306–322 [View Article]
    [Google Scholar]
  107. Briers Y, Staubli T, Schmid MC, Wagner M, Schuppler M et al. Intracellular vesicles as reproduction elements in cell wall-deficient L-form bacteria. PLoS One 2012; 7:e38514 [View Article] [PubMed]
    [Google Scholar]
  108. Siddiqui RA, Hoischen C, Holst O, Heinze I, Schlott B et al. The analysis of cell division and cell wall synthesis genes reveals mutationally inactivated ftsQ and mraY in a protoplast-type L-form of Escherichia coli. FEMS Microbiol Lett 2006; 258:305–311 [View Article] [PubMed]
    [Google Scholar]
  109. Dörr T, Alvarez L, Delgado F, Davis BM, Cava F et al. A cell wall damage response mediated by a sensor kinase/response regulator pair enables beta-lactam tolerance. Proc Natl Acad Sci USA 2016; 113:404–409 [View Article]
    [Google Scholar]
  110. Islam N, Kazi MI, Kang KN, Biboy J, Gray J et al. Peptidoglycan recycling promotes outer membrane integrity and carbapenem tolerance in Acinetobacter baumannii. mBio 2022; 13:e01001-22
    [Google Scholar]
  111. Murtha AN, Kazi MI, Schargel RD, Cross T, Fihn C et al. High-level carbapenem tolerance requires antibiotic-induced outer membrane modifications. PLoS Pathog 2022; 18:e1010307 [View Article] [PubMed]
    [Google Scholar]
  112. Guo X-P, Sun Y-C. New insights into the non-orthodox two component Rcs phosphorelay system. Front Microbiol 2017; 8:2014 [View Article]
    [Google Scholar]
  113. Majdalani N, Gottesman S. The Rcs phosphorelay: a complex signal transduction system. Annu Rev Microbiol 2005; 59:379–405 [View Article] [PubMed]
    [Google Scholar]
  114. Van Acker H, Coenye T. The role of reactive oxygen species in antibiotic-mediated killing of bacteria. Trends Microbiol 2017; 25:456–466 [View Article] [PubMed]
    [Google Scholar]
  115. Zhao X, Drlica K. Reactive oxygen species and the bacterial response to lethal stress. Curr Opin Microbiol 2014; 21:1–6 [View Article] [PubMed]
    [Google Scholar]
  116. Kawai Y, Mercier R, Wu LJ, Domínguez-Cuevas P, Oshima T et al. Cell growth of wall-free L-form bacteria is limited by oxidative damage. Curr Biol 2015; 25:1613–1618 [View Article]
    [Google Scholar]
  117. Fabijan AP, Kamruzzaman M, Martinez-Martin D, Venturini C, Mickiewicz K et al. L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli. bioRxiv 2021449206
    [Google Scholar]
  118. Huber TW, Brinkley AW. Growth of cell wall-defective variants of Escherichia coli: comparison of aerobic and anaerobic induction frequencies. J Clin Microbiol 1977; 6:166–171 [View Article]
    [Google Scholar]
  119. Seeberg S. Induction and surface growth of l-phase variants of different Escherichia coli strains. Acta Pathol Microbiol Scand B Microbiol Immunol 2009; 81B:703–706 [View Article]
    [Google Scholar]
  120. Han J, Shi W, Xu X, Wang S, Zhang S et al. Conditions and mutations affecting Staphylococcus aureus L-form formation. Microbiology 2015; 161:57–66 [View Article]
    [Google Scholar]
  121. Nwugo CC, Gaddy JA, Zimbler DL, Actis LA. Deciphering the iron response in Acinetobacter baumannii: proteomics approach. J Proteomics 2011; 74:44–58 [View Article] [PubMed]
    [Google Scholar]
  122. Nimmo LN, Blazevic DJ. Selection of media for the isolation of common bacterial L-phase organisms from a clinical specimen. Appl Microbiol 1969; 18:535–541 [View Article] [PubMed]
    [Google Scholar]
  123. Kawai Y, Mercier R, Errington J. Bacterial cell morphogenesis does not require a preexisting template structure. Curr Biol 2014; 24:863–867 [View Article] [PubMed]
    [Google Scholar]
  124. Ranjit DK, Jorgenson MA, Young KD. PBP1B glycosyltransferase and transpeptidase activities play different essential roles during the de novo regeneration of rod morphology in Escherichia coli. J Bacteriol 2017; 199:e00612-16 [View Article]
    [Google Scholar]
  125. Wang Y. The function of OmpA in Escherichia coli. Biochem Biophys Res Commun 2002; 292:396–401 [View Article] [PubMed]
    [Google Scholar]
  126. Szczepaniak J, Holmes P, Rajasekar K, Kaminska R, Samsudin F et al. The lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism. Nat Commun 2020; 11:1305 [View Article]
    [Google Scholar]
  127. Mathelié-Guinlet M, Asmar AT, Collet J-F, Dufrêne YF. Lipoprotein Lpp regulates the mechanical properties of the E. coli cell envelope. Nat Commun 2020; 11:1789 [View Article] [PubMed]
    [Google Scholar]
  128. Gumpert J, Taubeneck U. Modes of multiplication in an unstable spheroplast type F-form of Escherichia coli K12(lambda). Z Allg Mikrobiol 1974; 14:675690. [View Article] [PubMed]
    [Google Scholar]
  129. Green MT, Heidger PM, Domingue G. Proposed reproductive cycle for a relatively stable L-phase variant of Streptococcus faecalis. Infect Immun 1974; 10:915–927 [View Article] [PubMed]
    [Google Scholar]
  130. Studer P, Staubli T, Wieser N, Wolf P, Schuppler M et al. Proliferation of Listeria monocytogenes L-form cells by formation of internal and external vesicles. Nat Commun 2016; 7:13631 [View Article] [PubMed]
    [Google Scholar]
  131. Mercier R, Domínguez-Cuevas P, Errington J. Crucial role for membrane fluidity in proliferation of primitive cells. Cell Rep 2012; 1:417–423 [View Article] [PubMed]
    [Google Scholar]
  132. Vedyaykin AD, Ponomareva EV, Khodorkovskii MA, Borchsenius SN, Vishnyakov IE. Mechanisms of bacterial cell division. Microbiol 2019; 88:245–260 [View Article]
    [Google Scholar]
  133. Burmeister HR, Hesseltine CW. Induction and propagation of a Bacillus subtilis L form in natural and synthetic media. J Bacteriol 1968; 95:1857–1861 [View Article] [PubMed]
    [Google Scholar]
  134. Dienes L. Morphology and reproductive processes of the L forms of bacteria. I. Streptococci and straphylocci. J Bacteriol 1967; 93:693–702 [View Article]
    [Google Scholar]
  135. Briers Y, Walde P, Schuppler M, Loessner MJ. How did bacterial ancestors reproduce? Lessons from L-form cells and giant lipid vesicles: multiplication similarities between lipid vesicles and L-form bacteria. Bioessays 2012; 34:1078–1084 [View Article] [PubMed]
    [Google Scholar]
  136. Mercier R, Kawai Y, Errington J. Excess membrane synthesis drives a primitive mode of cell proliferation. Cell 2013; 152:997–1007 [View Article] [PubMed]
    [Google Scholar]
  137. Onwuamaegbu ME, Belcher RA, Soare C. Cell wall-deficient bacteria as a cause of infections: a review of the clinical significance. J Int Med Res 2005; 33:1–20 [View Article] [PubMed]
    [Google Scholar]
  138. Woo PC, Wong SS, Lum PN, Hui WT, Yuen KY. Cell-wall-deficient bacteria and culture-negative febrile episodes in bone-marrow-transplant recipients. Lancet 2001; 357:675–679 [View Article] [PubMed]
    [Google Scholar]
  139. Lapinski EM, Flakas ED. Induction of L forms of Haemophilus influenzae in culture and their demonstration in human bronchial secretions. J Bacteriol 1967; 93:1438–1445 [View Article] [PubMed]
    [Google Scholar]
  140. Landersdorfer CB, Nation RL. Limitations of antibiotic MIC-based PK-PD metrics: looking back to move forward. Front Pharmacol 2021; 12:770518 [View Article] [PubMed]
    [Google Scholar]
  141. Wen X, Gehring R, Stallbaumer A, Riviere JE, Volkova VV. Limitations of MIC as sole metric of pharmacodynamic response across the range of antimicrobial susceptibilities within a single bacterial species. Sci Rep 2016; 6:37907 [View Article] [PubMed]
    [Google Scholar]
  142. Markova N, Michailova L, Jourdanova M, Kussovski V, Valcheva V et al. Exhibition of persistent and drug-tolerant L-form habit of Mycobacterium tuberculosis during infection in rats. Open Life Sci 2008; 3:407–416 [View Article]
    [Google Scholar]
  143. Slavchev G, Michailova L, Markova N. L-form transformation phenomenon in Mycobacterium tuberculosis associated with drug tolerance to ethambutol. Int J Mycobacteriol 2016; 5:454–459 [View Article] [PubMed]
    [Google Scholar]
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