Antibiotic resistance of glycine-resistant variants of Staphylococcus aureus

1968 ◽  
Vol 14 (7) ◽  
pp. 811-812
Author(s):  
Joseph T. Parisi ◽  
William J. Suling
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Cross Resistance ◽  
Cell Wall Synthesis ◽  
Minimal Inhibitory Concentrations

Glycine-resistant variants of Staphylococcus aureus were obtained by successive cultivation of parent strains in increasing concentrations of glycine, and the minimal inhibitory concentrations of glycine of the parents and variants were determined. Although it has been reported that growth in glycine or certain antibiotics causes the accumulation of nucleotides involved in cell wall synthesis, a lack of cross resistance of the variants to some of these antibiotics was observed.

scholarly journals A Staphylococcus aureus clpX Mutant Used as a Unique Screening Tool to Identify Cell Wall Synthesis Inhibitors that Reverse β-Lactam Resistance in MRSA

2021 ◽  
Vol 8 ◽  
Author(s):  
Kristoffer T. Bæk ◽  
Camilla Jensen ◽  
Maya A. Farha ◽  
Tobias K. Nielsen ◽  
Ervin Paknejadi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
High Throughput Screening ◽  
Bacterial Infections ◽  
Screening Tool ◽  
Acquired Resistance ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Biologically Active ◽  
Cell Wall Synthesis

Staphylococcus aureus is a leading cause of bacterial infections world-wide. Staphylococcal infections are preferentially treated with β-lactam antibiotics, however, methicillin-resistant S. aureus (MRSA) strains have acquired resistance to this superior class of antibiotics. We have developed a growth-based, high-throughput screening approach that directly identifies cell wall synthesis inhibitors capable of reversing β-lactam resistance in MRSA. The screen is based on the finding that S. aureus mutants lacking the ClpX chaperone grow very poorly at 30°C unless specific steps in teichoic acid synthesis or penicillin binding protein (PBP) activity are inhibited. This property allowed us to exploit the S. aureus clpX mutant as a unique screening tool to rapidly identify biologically active compounds that target cell wall synthesis. We tested a library of ∼50,000 small chemical compounds and searched for compounds that inhibited growth of the wild type while stimulating growth of the clpX mutant. Fifty-eight compounds met these screening criteria, and preliminary tests of 10 compounds identified seven compounds that reverse β-lactam resistance of MRSA as expected for inhibitors of teichoic acid synthesis. The hit compounds are therefore promising candidates for further development as novel combination agents to restore β-lactam efficacy against MRSA.

scholarly journals Role of the msaABCR Operon in Cell Wall Biosynthesis, Autolysis, Integrity, and Antibiotic Resistance in Staphylococcus aureus

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Bibek G C ◽  
Gyan S. Sahukhal ◽  
Mohamed O. Elasri
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Teichoic Acid ◽  
Cross Linking ◽  
Wall Defect ◽  
Content Type ◽  
Mrsa Strains ◽  
Mutant Cells

ABSTRACT Staphylococcus aureus is an important human pathogen in both community and health care settings. One of the challenges with S. aureus as a pathogen is its acquisition of antibiotic resistance. Previously, we showed that deletion of the msaABCR operon reduces cell wall thickness, resulting in decreased resistance to vancomycin in vancomycin-intermediate S. aureus (VISA). In this study, we investigated the nature of the cell wall defect in the msaABCR operon mutant in the Mu50 (VISA) and USA300 LAC methicillin-resistant Staphylococcus aureus (MRSA) strains. Results showed that msaABCR mutant cells had decreased cross-linking in both strains. This defect is typically due to increased murein hydrolase activity and/or nonspecific processing of murein hydrolases mediated by increased protease activity in mutant cells. The defect was enhanced by a decrease in teichoic acid content in the msaABCR mutant. Therefore, we propose that deletion of the msaABCR operon results in decreased peptidoglycan cross-linking, leading to increased susceptibility toward cell wall-targeting antibiotics, such as β-lactams and vancomycin. Moreover, we also observed significantly downregulated transcription of early cell wall-synthesizing genes, supporting the finding that msaABCR mutant cells have decreased peptidoglycan synthesis. More specifically, the msaABCR mutant in the USA300 LAC strain (MRSA) showed significantly reduced expression of the murA gene, whereas the msaABCR mutant in the Mu50 strain (VISA) showed significantly reduced expression of glmU, murA, and murD. Thus, we conclude that the msaABCR operon controls the balance between cell wall synthesis and cell wall hydrolysis, which is required for maintaining a robust cell wall and acquiring resistance to cell wall-targeting antibiotics, such as vancomycin and the β-lactams.

scholarly journals Carriage Methicillin-Resistant Staphylococcus aureus in Poultry and Cattle in Northern Algeria

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Saliha Bounar-Kechih ◽  
Mossadak Taha Hamdi ◽  
Hebib Aggad ◽  
Nacima Meguenni ◽  
Zafer Cantekin
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Broiler Chickens ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Laying Hens ◽  
Methicillin Resistance ◽  
Public Health Problem ◽  
Cross Resistance ◽  
Isolation And Identification ◽  
Methicillin Resistant

Multiresistant and especially Methicillin-Resistant Staphylococcus aureus (MRSA) poses a serious public health problem that requires their immediate identification and antibiotic resistance characteristics. In order to determine antibiotic resistance S. aureus poultry and bovine origin, 8840 samples were collected from slaughterhouses in the northern region of Algeria between years 2009 and 2014. 8375 samples were from an avian origin (1875 from laying hens and 6500 from broiler chickens) and the rest was from bovine origin. Bacteriological isolation and identification were made by classical culture method and antibiotic resistance patterns were determined by disc diffusion test. The prevalence of S. aureus was 42% in laying hens, 12% in broilers, and 55% in bovine samples. The prevalence of MRSA was 57%, 50%, and 31% in laying hens, broiler chickens, and bovine, respectively. While MRSA strains isolated from poultry showed cross-resistance to aminoglycosides, fluoroquinolones, macrolides, sulphonamides, and cyclins, those isolated from bovine also revealed similar multiresistance except for sulphonamide. This high percentage of methicillin resistance and multidrug resistance in S. aureus poultry and bovine origin may have importance for human health and curing of human infections.

scholarly journals High-Level β-Lactam Resistance and Cell Wall Synthesis Catalyzed by the mecA Homologue of Staphylococcus sciuri Introduced into Staphylococcus aureus

2005 ◽  
Vol 187 (19) ◽  
pp. 6651-6658 ◽  
Author(s):  
Anatoly Severin ◽  
Shang Wei Wu ◽  
Keiko Tabei ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
High Performance ◽  
Protein Product ◽  
Spectrometric Analysis ◽  
Cell Wall Synthesis ◽  
Absolute Dependence ◽  
A Cell ◽  
High Concentrations ◽  
High Level

ABSTRACT A close homologue of mecA, the determinant of broad-spectrum β-lactam resistance in Staphylococcus aureus was recently identified as a native gene in the animal commensal species Staphylococcus sciuri. Introduction of the mecA homologue from a methicillin-resistant strain of S. sciuri into a susceptible strain of S. aureus caused an increase in drug resistance and allowed continued growth and cell wall synthesis of the bacteria in the presence of high concentrations of antibiotic. We determined the muropeptide composition of the S. sciuri cell wall by using a combination of high-performance liquid chromatography, mass spectrometric analysis, and Edman degradation. Several major differences between the cell walls of S. aureus and S. sciuri were noted. The pentapeptide branches in S. sciuri were composed of one alanine and four glycine residues in contrast to the pentaglycine units in S. aureus. The S. sciuri wall but not the wall of S. aureus contained tri- and tetrapeptide units, suggesting the presence of dd- and ld-carboxypeptidase activity. Most interestingly, S. aureus carrying the S. sciuri mecA and growing in methicillin-containing medium produced a cell wall typical of S. aureus and not S. sciuri, in spite of the fact that wall synthesis under these conditions had an absolute dependence on the heterologous S. sciuri gene product. The protein product of the S. sciuri mecA can efficiently participate in cell wall biosynthesis and build a cell wall using the cell wall precursors characteristic of the S. aureus host.

scholarly journals CELL WALL SYNTHESIS BY STAPHYLOCOCCUS AUREUS IN THE PRESENCE OF PROTEIN SYNTHESIS INHIBITORY AGENTS

1972 ◽  
Vol 25 (11) ◽  
pp. 679-680 ◽  
Author(s):  
EIRYO KITANAKA ◽  
KAZUYORI OCHIAI ◽  
YASUHISA HAMASU ◽  
MASAFUMI NAKAO ◽  
SHOZO NAKAZAWA
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Protein Synthesis ◽  
Cell Wall Synthesis ◽  
Inhibitory Agents

The gate controlling cell wall synthesis in Staphylococcus aureus

2004 ◽  
Vol 53 (4) ◽  
pp. 1221-1231 ◽  
Author(s):  
Hitoshi Komatsuzawa ◽  
Tamaki Fujiwara ◽  
Hiromi Nishi ◽  
Sakuo Yamada ◽  
Masaru Ohara ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Wall Synthesis

scholarly journals Staphylococcus aureus Cell Wall Biosynthesis Modulates Bone Invasion and Osteomyelitis Pathogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Elysia A. Masters ◽  
Gowrishankar Muthukrishnan ◽  
Lananh Ho ◽  
Ann Lindley Gill ◽  
Karen L. de Mesy Bentley ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Surface Protein ◽  
Implant Loosening ◽  
Penicillin Binding Protein ◽  
Cell Wall Synthesis ◽  
Transmission Electron ◽  
Surface Adhesins

Staphylococcus aureus invasion of the osteocyte lacuno-canalicular network (OLCN) is a novel mechanism of bacterial persistence and immune evasion in chronic osteomyelitis. Previous work highlighted S. aureus cell wall transpeptidase, penicillin binding protein 4 (PBP4), and surface adhesin, S. aureus surface protein C (SasC), as critical factors for bacterial deformation and propagation through nanopores in vitro, representative of the confined canaliculi in vivo. Given these findings, we hypothesized that cell wall synthesis machinery and surface adhesins enable durotaxis- and haptotaxis-guided invasion of the OLCN, respectively. Here, we investigated select S. aureus cell wall synthesis mutants (Δpbp3, Δatl, and ΔmreC) and surface adhesin mutants (ΔclfA and ΔsasC) for nanopore propagation in vitro and osteomyelitis pathogenesis in vivo. In vitro evaluation in the microfluidic silicon membrane-canalicular array (μSiM-CA) showed pbp3, atl, clfA, and sasC deletion reduced nanopore propagation. Using a murine model for implant-associated osteomyelitis, S. aureus cell wall synthesis proteins were found to be key modulators of S. aureus osteomyelitis pathogenesis, while surface adhesins had minimal effects. Specifically, deletion of pbp3 and atl decreased septic implant loosening and S. aureus abscess formation in the medullary cavity, while deletion of surface adhesins showed no significant differences. Further, peri-implant osteolysis, osteoclast activity, and receptor activator of nuclear factor kappa-B ligand (RANKL) production were decreased following pbp3 deletion. Most notably, transmission electron microscopy (TEM) imaging of infected bone showed that pbp3 was the only gene herein associated with decreased submicron invasion of canaliculi in vivo. Together, these results demonstrate that S. aureus cell wall synthesis enzymes are critical for OLCN invasion and osteomyelitis pathogenesis in vivo.

Cell-Wall Synthesis by Staphylococcus Aureus in the Presence of Chloramphenicol

Nature ◽  
1958 ◽  
Vol 181 (4615) ◽  
pp. 1050-1052 ◽  
Author(s):  
R. HANCOCK ◽  
JAMES T. PARK
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Wall Synthesis

scholarly journals CELL WALL SYNTHESIS BY STAPHYLOCOCCUS AUREUS IN THE PRESENCE OF PROTEIN SYNTHESIS INHIBITORY AGENTS

1972 ◽  
Vol 25 (8) ◽  
pp. 469-470 ◽  
Author(s):  
MASAFUMI NAKAO ◽  
EIRYO KITANAKA ◽  
KAZUYORI OCHIAI ◽  
SHOZO NAKAZAWA
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Protein Synthesis ◽  
Cell Wall Synthesis ◽  
Inhibitory Agents
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