Properties of Proteus mirabilis and Providence Spheroplasts

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

“…This transition from filaments to spheroplasts or lysis also increases with duration of antibiotic exposure [55]. The β-lactam induced formation of filaments occurs, not just in E. coli and P. aeruginosa, but in many species of Gram-negative bacteria [49,53,65,74,81,[121][122][123] and a limited number of Gram-positive bacteria [124][125][126]. In most cases it is bacilli that are affected, but filamentation has also been reported in some species of cocci [124,125,127], specifically those in the Streptococcus genus, which divide in just one plane.…”

“…Lysozyme, which enzymatically degrades peptidoglycan by hydrolysing the glycosidic bonds between N-acetyl muramic acid and N-acetyl-D-glucosamine, causes protoplast formation in Grampositive cells [92]. In Gram-negative bacteria, peptidoglycan is shielded by the outer membrane [93], and lysozyme cannot induce spheroplast formation unless a membrane permeabilizer such as lactoferrin or EDTA is also present [74,92,94]. Other peptidoglycan hydrolyzing enzymes that induce protoplast formation include N,O-diacetylmuramidase [95] and lysostaphin [96].…”

“…For β-lactams which preferentially target E. coli PBP2 and/or PBP3, other morphological changes ('ovoid cells', 'localized swelling' and 'filaments') occur at low antibiotic concentrations, with spheroplasts only becoming evident when antibiotic concentration is increased to a point where PBPs 1a and 1b become bound [76,78]. The β-lactam induced formation of spheroplasts and protoplasts occurs, not just in E. coli, but in many species of Gram-negative [36, 53,74,[79][80][81][82][83] and Gram-positive bacteria [69,84]. However, because PBP nomenclature is species-dependent [85,86], and because relatively few studies have determined the affinity of their test β-lactam(s) for the PBPs of their test species, the relationship between spheroplast formation and inhibition of a specific PBP is less clearly defined for these species than E.…”

“…Examples of spheroplast-inducing disruptors of peptidoglycan synthesis outside the β-lactam class include the MurA inhibitor fosfomycin [73], the MurC inhibitor glycine [74,87], the Alr and Ddl inhibitor cycloserine [73], the MraY inhibitor mureidomycin [73,88], the D-alanyl-D-alanine binding antibiotic vancomycin [89], the transglycosylase inhibitors ensanchomycin, prenomycin [73], and moenomycin [90], and the transpeptidase inhibitor lactivicin [91]. Depriving cells of diaminopimelic acid [57] or inhibiting its incorporation into the cell wall using malioxamycin [73] also triggers spheroplast formation.…”

“…1) [61]. Because they lack a peptidoglycan layer, spheroplasts and protoplasts are osmotically sensitive and rapidly lyse when transferred to hypotonic media [53,74].…”