Role of the msaABCR operon in cell wall biosynthesis, autolysis, integrity, and antibiotic resistance in Staphylococcus aureus.

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 crosslinking 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 crosslinking, leading to increased susceptibility towards 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. PMID: 31307991 [PubM...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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In conclusion, contrary to the situation in vitro, AZM was effective against MRSA growth in vivo in our pneumonia model, substantially improving survival. The suppressive effect on MRSA growth at the initial stage of pneumonia could underlie the potential mechanism of AZM action against MRSA pneumonia. PMID: 31235625 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Authors: Wang S, Li Y, Xue F, Liu J, Yang W, Zhang J, Glenschek-Sieberth M, Lyu Y Abstract We compared the kill-curve activity of tedizolid and linezolid at clinically relevant (total or free plasma, lung) concentrations against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) isolated from Chinese patients. Tedizolid had greater in vitro potency than linezolid against staphylococci, streptococci and enterococci species (tedizolid minimum inhibitory concentration (MIC) range: ≤ 0.016-0.5 µg/mL; linezolid MIC range: 0.25-2 µg/mL)...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Abstract Methicillin-resistant Staphylococcus aureus (MRSA) strains that are resistant to all forms of penicillin have become an increasingly common and urgent problem threatening human health. They are responsible for a wide variety of infectious diseases ranging from minor skin abscesses to life-threatening severe infections. The vra operon that is conserved among S. aureus strains encodes a three-component signal transduction system (vraTSR) that is responsible for sensing and responding to cell-wall stress. We developed a novel and multi-faceted assay to identify compounds that potentiate the activity of oxaci...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Staphylococcus aureus strains that possess a mecA gene but are phenotypically susceptible to oxacillin and cefoxitin (OS-MRSA) have been recognized for over a decade and are a challenge for diagnostic laboratories. The mechanisms underlying the discrepancy vary from isolate to isolate. We characterized seven OS-MRSA clinical isolates of six different spa types from six different states by whole genome sequencing (WGS) to identify the nucleotide sequence changes leading to the OS-MRSA phenotype. The results demonstrated that oxacillin susceptibility was associated with mutations in regions of nucleotide re...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance? Maria S. Zharkova1, Dmitriy S. Orlov1, Olga Yu. Golubeva2, Oleg B. Chakchir3, Igor E. Eliseev3, Tatyana M. Grinchuk4 and Olga V. Shamova1* 1Laboratory of Design and Synthesis of Biologically Active Peptides, Department of General Pathology and Pathophysiology, FSBSI Institute of Experimental Medicine, Saint Petersburg, Russia 2Laboratory of Nanostructures Research, Institute of Silicate Chemistry of the Russian Academy of Sciences, Saint Petersburg, Russia ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Abstract Bloodstream infection (BSI) organisms were consecutively collected from>200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. The most common pathogen overall was Staphylococcus aureus (20.7%), followed by Escherichia coli (20.5%), Klebsiella pneumoniae (7.7%), Pseudomonas aeruginosa (5.3%), and Enterococcus faecalis (5.2%). S. aureus was the most frequent pathogen overall in th...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics. Antimicrob Agents Chemother. 2019 Apr 22;: Authors: Ersoy SC, Abdelhady W, Li L, Chambers HF, Xiong YQ, Bayer AS Abstract Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as 'resistant' to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strai...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Vancomycin (VAN) and daptomycin (DAP) are approved as monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up front DAP+CPT head-to-head vs. standard monotherapy as initial treatment.In a pilot study, we evaluated 40 adult patients who were randomized to receive DAP 6-8 mg/kg/d + CPT 600 mg IV q8 h (n=17) or standard monotherapy (n=23) with vancomycin (VAN, dosed to achieve serum trough concentrations 15-20 mg/L, n=21) or ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
ang M Abstract The quinazolinones are a new class of antibacterials with in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA). The quinazolinones target cell-wall biosynthesis and have a unique mechanism of action by binding to the allosteric site of penicillin-binding protein (PBP)2a. We investigated the potential for synergism of a lead quinazolinone with several antibiotics of different classes using the checkerboard and time-kill assays. The quinazolinone synergized with β-lactam antibiotics. The combination of the quinazolinone with the commercial piperacillin-tazobactam showed bac...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
This study updates the distribution and trends of Gram-positive organisms causing bloodstream infections (BSIs) in the United States (US) and Europe during 2010-2016. In vitro activities of oritavancin and comparators were also evaluated. Staphylococcus aureus, Enterococcus spp., and coagulase-negative staphylococci (CoNS) were the most common organisms in both regions. The proportion of methicillin-resistant S. aureus (MRSA) among all isolates declined (from 11.5% to 9.9%) in the US, a trend also noted for methicillin resistance rates within S. aureus (from 45.7% to 41.9%). MRSA rates (4.1% to 4.2%) in Europe remained sta...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
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