Methicillin-resistant septal peptidoglycan synthesis in a methicillin-resistant Staphylococcus aureus strain

Wilkinson, Brian J.; Nadakavukaren, M J

doi:10.1128/aac.23.4.610

Cited by 18 publications

(16 citation statements)

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“…The response of peptidoglycan synthesis to methicillin in chloramphenicol-inhibited cultures, in which no induction of PBP 2' production by the challenging methicillin can occur (5), showed the same pattern. However, the peptidoglycan synthesis occurring in chloramphenicol-inhibited cultures is believed to represent wall thickening rather than septal peptidoglycan synthesis (24,29). Nevertheless, these results provide supporting evidence for the supposition that PBP 2' represents a ,-lactam-insensitive peptidoglycan transpeptidase which al- At 30°C, growth with NaCl clearly increased PBP 2' production but peptidoglycan synthesis was no more methicillin resistant.…”

Section: Resultscontrasting

confidence: 39%

“…However, such cells were not growing normaily. Their peptidoglycan was poorly cross-linked (18,31), their septa were enlarged, and their division was aberrant (29). Perhaps growth eventually stops because the normal synthesis and maturation of peptidoglycan is interfered with, even though PBP 2' may be capable of synthesizing more peptidoglycan.…”

Section: Resultsmentioning

confidence: 99%

“…Strain DU4916 is a relatively extensively studied, homogeneous, methicillin-resistant strain (8,15,18,24,29), and strain DU4916-K7 is a less-well-studied derivative produced by acriflavine treatment of strain DU4916 (8). In Table 1, MICs and population analyses of strains DU4916 and DU4916-K7 under different growth conditions are shown.…”

Section: Resultsmentioning

confidence: 99%

“…Wilkinson, M. V. V. S. Madiraju, and D. P. Brunner, Clinical Implications ofAntimicrobial Resistance, in press), although few studies have attempted to examine this (4,24,31). Studies of the lytic properties (18,29), genetics (2), and resistance expression (11) of methicillin-resistant S. aureus have raised the possibility that PBP 2' production alone is not the entire explanation of methicillin resistance. Re-cently, Berger-Bachi et al (3) reported that a methicillinsusceptible strain derived from a methicillin-resistant strain by insertion of transposon TnS51 still produced PBP 2'.…”

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confidence: 99%

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Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus

Madiraju

Brunner

Wilkinson

1987

Antimicrob Agents Chemother

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Methicillin-resistant Staphylococcus aureus strains produce a fifth penicillin-binding protein (PBP), PBP 2', with low affinity for I-lactam antibiotics that is believed to represent a P-lactam-insensitive peptidoglycan transpeptidase. In an effort to evaluate the adequacy of PBP 2' as an explanation of methicillin resistance, PBP 2' production and the responses of growth and peptidoglycan synthesis to methicillin under different environmental conditions have been compared. In the heterogeneous methicillin-resistant strain DU4916-K7, less PBP 2' was produced at 40°C than at 30°C, but inclusion of 5% (wt/vol) NaCl in the medium at 40°C boosted PBP 2' production and allowed growth of the organism in the presence of 10 ,ug of methicillin per ml. When exponential-phase cultures were challenged with methicillin, growth and peptidoglycan synthesis were much more resistant at 30°C than at 40°C. Inclusion of NaCl in medium rendered growth and peptidoglycan synthesis more methicillin resistant at 40°C. Hence, there was a good correlation between PBP 2' production and methicillin-resistant peptidoglycan synthesis under these conditions. However, PBP 2' production was increased by NaCI at 30°C without markedly affecting the susceptibilities of growth and peptidoglycan synthesis to methicillin. Pregrowth of cells with methicillin, which was expected to boost PBP 2' production, seemed to increase the susceptibilities of growth and peptidoglycan synthesis to methicillin. Patterns of growth and peptidoglycan synthesis susceptibilities to methicillin which were similar to those described above were found in chloramphenicol-inhibited cultures, in which presumably no induction of PBP 2' could occur during the methicillin challenge period. Complex effects were noted in the combination of subinhibitory methicillin and NaCl. Growth of cells in the presence of NaCl stimulated their autolytic activity, which was further increased by growth with subinhibitory methicillin in addition to NaCl. It appears that NaCl enhances methicillin resistance by stimulating PBP 2' production and providing osmotic support but opposes it by stimulating autolytic activity which is exacerbated by the very low cross-linking of peptidoglycan in methicillin-resistant strains grown in the presence of methicillin.

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Section: Resultscontrasting

confidence: 39%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus

Madiraju

Brunner

Wilkinson

1987

Antimicrob Agents Chemother

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“…Electron micrographic studies of a methicillin-resistant strain grown in methicillin revealed thickened septa, attributed to unbalanced growth and diversion of cell wall material into the septum at the expense of the peripheral, nonseptal wall (171 (114,157). The National Committee for Clinical Laboratory Standards currently recommends the use of 2% NaCl, an inoculum of 5 x 105 CFU/ml, and incubation for 24 h at a temperature of 350C.…”

Section: Other Factorsmentioning

confidence: 99%

Methicillin-resistant staphylococci

1988

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Strains of staphylococci resistant to methicillin were identified immediately after introduction of this drug. Methicillin-resistant strains have unusual properties, the most notable of which is extreme variability in expression of the resistance trait. The conditions associated with this heterogeneous expression of resistance are described. Methicillin resistance is associated with production of a unique penicillin-binding protein (PBP), 2a, which is bound and inactivated only at high concentrations of beta-lactam antibiotics. PBP2a appears to be encoded by the mec determinant, which also is unique to methicillin-resistant strains. The relationships between PBP2a and expression of resistance and implications for the mechanism of resistance are discussed. The heterogeneous expression of methicillin resistance by staphylococci poses problems in the detection of resistant strains. Experience with several susceptibility test methods is reviewed and guidelines for performance of these tests are given. Treatment of infections caused by methicillin-resistant staphylococci is discussed. Vancomycin is the treatment of choice. Alternatives have been few because methicillin-resistant strains often are resistant to multiple antibiotics in addition to beta-lactam antibiotics. New agents which are active against methicillin-resistant staphylococci are becoming available, and their potential role in treatment is discussed.

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The Isolation ofStaphylococcus aureusTea Tree Oil-Reduced Susceptibility Mutants

et al. 2014

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Tea tree oil-reduced susceptibility (TTORS) mutants of two Staphylococcus aureus laboratory strains were isolated utilizing TTO gradient plates. Attempts to isolate TTORS mutants employing agar plates containing single TTO concentrations failed. All TTORS mutants demonstrated a small colony variant (SCV) phenotype and produced cells with a smaller diameter, as determined by scanning electron microscopy. The addition of SCV auxotrophic supplements to media did not lead to an increase in TTORS mutant colony size. TTORS mutant revertants (RV) were also isolated from the TTORS mutants following growth in drug free media and all RV strains demonstrated phenotypes similar to their respective parent strains. Transmission electron microscopy revealed that a SH1000 TTORS mutant demonstrated a thinner cell wall and novel septal invaginations compared to parent strain SH1000. In addition, comparative genomic sequencing did not reveal any mutations in a SH1000 TTORS mutant previously linked to well-characterized SCV genotypes. This study demonstrates that TTO can select for a unique SCV phenotype.

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Methicillin-resistant septal peptidoglycan synthesis in a methicillin-resistant Staphylococcus aureus strain

Cited by 18 publications

References 14 publications

Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus

Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus

Methicillin-resistant staphylococci

The Isolation ofStaphylococcus aureusTea Tree Oil-Reduced Susceptibility Mutants

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