Vancomycin adsorption to Bacillus subtilis cell walls

Best, Gary K.; Durham, Norman N.

doi:10.1016/0003-9861(65)90250-x

Cited by 47 publications

(26 citation statements)

References 12 publications

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“…Some of the properties of the highly vancomycin-resistant S. aureus mutant VM described in this communication have also been seen in other bacteria, such as binding of vancomycin to bacterial cell walls (1,4,24,27), abnormal morphology and the appearance of amorphous material on the surface of glycopeptide-treated bacteria (29,41), and the capacity of some lowlevel vancomycin-resistant laboratory mutants and/or clinical isolates of coagulase-negative staphylococci to remove vancomycin from the growth medium (25,30). Whether the mechanism of resistance of these low-level vancomycin-resistant staphylococci is similar to the mechanism we propose for the highly vancomycin-resistant S. aureus described in this communication remains to be tested.…”

Section: Discussionmentioning

confidence: 55%

Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

1997

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A highly vancomycin-resistant mutant (MIC ‫؍‬ 100 g/ml) of Staphylococcus aureus, mutant VM, which was isolated in the laboratory by a step-pressure procedure, continued to grow and synthesize peptidoglycan in the presence of vancomycin (50 g/ml) in the medium, but the antibiotic completely inhibited cell wall turnover and autolysis, resulting in the accumulation of cell wall material at the cell surface and inhibition of daughter cell separation. Cultures of mutant VM removed vancomycin from the growth medium through binding the antibiotic to the cell walls, from which the antibiotic could be quantitatively recovered in biologically active form. Vancomycin blocked the in vitro hydrolysis of cell walls by autolytic enzyme extracts, lysostaphin and mutanolysin. Analysis of UDP-linked peptidoglycan precursors showed no evidence for the presence of Dlactate-terminating muropeptides. While there was no significant difference in the composition of muropeptide units of mutant and parental cell walls, the peptidoglycan of VM had a significantly lower degree of crosslinkage. These observations and the results of vancomycin-binding studies suggest alterations in the structural organization of the mutant cell walls such that access of the vancomycin molecules to the sites of wall biosynthesis is blocked.Multidrug-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) in which the therapeutic choice is often reduced to a small number of antibiotics, primarily vancomycin, have spread worldwide during the late 1980s and mid1990s. The appearance of vancomycin resistance among clinical isolates of enterococci has raised concern about transfer of the resistance genes to highly virulent strains of MRSA with obvious dire implications for chemotherapy. While current concern is directed primarily to interspecific transfer of enterococcal resistance genes, attention has also been paid to other, alternative vancomycin resistance mechanisms that may emerge among S. aureus and coagulase-negative strains of nosocomial staphylococci as a consequence of the extensive use of vancomycin in the hospital environment worldwide (for a review, see reference 42). Moderately increased vancomycin (and teicoplanin) MICs have indeed been noted among some clinical isolates of coagulase-negative staphylococci (3,6,20,31,32,40), and glycopeptide-resistant variants or mutants of staphylococci have also been isolated in several laboratories by the usual step-pressure procedures (5,7,8,16,18,40).While studying the effect of cell wall synthesis inhibitors on the expression of methicillin resistance in S. aureus, we observed rare staphylococcal cells that were able to form colonies on agar containing 6 and even 12 g of vancomycin per ml. Serial passages of such colonies in vancomycin-containing media (step-pressure procedure) resulted in the emergence of stable variants (mutants) with even higher levels of vancomycin resistance. One mutant for which the vancomycin MIC was 100 g/ml had the unique capacity to quantitatively remove vancomycin f...

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Section: Discussionmentioning

confidence: 55%

Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

1997

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“…Furthermore, the addition of additional divalent cations to the medium (including Mn and Mg) still resulted in citrate-mediated stimulation of biofilm formation (62). However, both vancomycin and bacitracin require divalent cations to be effective, and the antimicrobial capacity of bacitracin is reported to be inhibited by citrate, suggesting that citrate inhibits these antibiotics through the sequestration of cations (1,7,8,58). Furthermore, since emerging glycopeptide resistance in S. aureus is an important concern for human health (2), we chose to test glycopeptide resistance determinants as potential regulators of citrate-stimulated biofilm formation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Evidence for an Alternative Citrate-Dependent Biofilm Formation Pathway in Staphylococcus aureus That Is Dependent on Fibronectin Binding Proteins and the GraRS Two-Component Regulatory System

et al. 2008

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We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several other tricarboxylic acid (TCA) cycle intermediates in an FnbA-dependent fashion. While aconitase contributes to biofilm formation in the absence of TCA cycle intermediates, it is not required for biofilm stimulation by these compounds. Furthermore, the GraRS two-component regulator and the GraRS-regulated efflux pump VraFG, identified for their roles in intermediate vancomycin resistance, are required for citrate-stimulated cell-to-cell interactions, but the GraRS regulatory system does not impact the expression of the fnbA and fnbB genes. Our data suggest that distinct genetic factors are required for the early steps in citrate-stimulated biofilm formation. Given the role of FnbA/FnbB and SarA in virulence in vivo and the lack of a role for ica-mediated biofilm formation in S. aureus catheter models of infection, we propose that the citrate-stimulated biofilm formation pathway may represent a clinically relevant pathway for the formation of these bacterial communities on medical implants.Microorganisms commonly adhere to surfaces in multilayered groupings referred to as biofilms (29,54). Growth in a biofilm imparts particular properties to member organisms, including elevated levels of resistance to antibiotics and host defenses. Staphylococcus aureus, a common nosocomial pathogen known for its antibiotic resistance and its ability to cause a wide range of infections (43), can form biofilms on a number of medically relevant surfaces such as catheters and intraocular lenses (56,71,75). Biofilm formation by this microbe is thought to contribute to its ability to cause persistent infections (19,71,74).Most genetic studies of biofilm formation by S. aureus have involved the search for biofilm-defective mutants using laboratory medium, typically tryptic soy broth (TSB) supplemented with glucose. Such an approach has identified a number of genetic loci required for biofilm formation, including sarA, agr, dlt, hla, clp, and ica, which codes for the polysaccharide component of an extracellular biofilm matrix (9,25,27,45,55,66,72). The ica locus, its gene products, and the polysaccharide produced by the Ica proteins have been studied extensively in vitro (17, 44-46, 50, 53). A recent study reported a role for the ica locus of S. aureus in models of systemic infection and renal abscess infect...

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“…It is assumed that either the association of undecaprenyl-phosphate (reaction 2) or the dissociation E + CP -E.C5XP (2) E*C 5sP + UMPPMp UMPPMp *E*C55P (3) UMPPMp.E.C55P . UMP.E.C5,PPMp MP.E.C5PX (4) PMp UMP *E.C5,PPMp=: E.C,5PPMp + UMP (5) E.C,PPMp E + C55PPMp (6) of undecaprenyl-diphosphate-MurNAc-pentapeptide (reaction 6) is rate limiting (21 gg of vancomycin per ml and, in contrast to the transfer assay, no stimulation is observed. As in the case of the transfer assay, no effect by vancomycin is observed with UDP-MurNActetrapeptide.…”

Section: Discussionmentioning

confidence: 99%

“…An additional class of high-affinity binding sites for vancomycin exists on the cell wall (4 (17) estimated that 10% of the iodovancomycin was in the protoplast-membrane fraction. Thus, only a fraction of the antibiotic penetrates to the membrane to exert the 'fects found with the in vitro peptidoglycan-synthesizing system.…”

Section: Discussionmentioning

confidence: 99%

On the Mechanism of Action of Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari

Hammes

Neuhaus

1974

Antimicrob Agents Chemother

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Vancomycin adsorption to Bacillus subtilis cell walls

Cited by 47 publications

References 12 publications

Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

Genetic Evidence for an Alternative Citrate-Dependent Biofilm Formation Pathway in Staphylococcus aureus That Is Dependent on Fibronectin Binding Proteins and the GraRS Two-Component Regulatory System

On the Mechanism of Action of Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari

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