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

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 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.

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

scholarly journals LcpB Is a Pyrophosphatase Responsible for Wall Teichoic Acid Synthesis and Virulence in Staphylococcus aureus Clinical Isolate ST59

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Pan ◽  
Jing Guan ◽  
Yujie Li ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Molecular Mechanisms ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Cell Wall Synthesis ◽  
Wall Teichoic Acid ◽  
Independent Manner ◽  
Methicillin Resistant

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe pandemics primarily consisting of skin and soft tissue infections. However, the underlying pathomechanisms of the bacterium are yet to fully understood. The present study identifies LcpB protein, which belongs to the LytR-A-Psr (LCP) family, is crucial for cell wall synthesis and virulence in S. aureus. The findings revealed that LcpB is a pyrophosphatase responsible for wall teichoic acid synthesis. The results also showed that LcpB regulates enzyme activity through specific key arginine sites in its LCP domain. Furthermore, knockout of lcpB in the CA-MRSA isolate ST59 resulted in enhanced hemolytic activity, enlarged of abscesses, and increased leukocyte infiltration. Meanwhile, we also found that LcpB regulates virulence in agr-independent manner and the key sites for pyrophosphatase of LcpB play critical roles in regulating the virulence. In addition, the results showed that the role of LcpB was different between methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). This study therefore highlights the dual role of LcpB in cell wall synthesis and regulation of virulence. These insights on the underlying molecular mechanisms can thus guide the development of novel anti-infective strategies.

scholarly journals SmdA is a novel cell morphology determinant in Staphylococcus aureus

2021 ◽  
Author(s):  
Ine Storaker Myrbråten ◽  
Gro A. Stamsås ◽  
Helena Chan ◽  
Danae Morales Angeles ◽  
Tiril Mathiesen Knutsen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Division ◽  
Cell Morphology ◽  
Spherical Shape ◽  
Major Influence ◽  
Cell Wall Synthesis ◽  
Division Plane ◽  
Microscopy Techniques ◽  
Two Hybrid

Cell division and cell wall synthesis in staphylococci need to be precisely coordinated and controlled to allow the cell to multiply while maintaining their nearly spherical shape. The mechanisms ensuring correct placement of the division plane and synthesis of new cell wall have been studied intensively, however, hitherto unknown factors and proteins are likely to play key roles in this complex interplay. Starting from a subcellular localization- and gene knockdown screen of essential genes with unknown functions in Staphylococcus aureus, we identified a protein with major influence on cell morphology in S. aureus. The protein, here named SmdA (for staphylococcal morphology determinant A), is a membrane-protein with septum-enriched localization. By smdA silencing and overexpression, we have used different microscopy techniques to show that SmdA is critical for cell division, including septum formation and cell splitting. We also identified conserved residues in SmdA that are critical for functionality. Pulldown- and bacterial two-hybrid interaction experiments showed that SmdA interacts with several known cell division- and cell wall synthesis proteins, including penicillin binding proteins (PBPs) and EzrA. Notably, SmdA also affects susceptibility to cell wall targeting antibiotics, particularly in methicillin-resistant S. aureus (MRSA). Together, our results show that S. aureus is dependent on balanced amounts of membrane-attached SmdA in order to carry out proper cell division.

Sign in / Sign up

Export Citation Format

Share Document