scholarly journals Significant Variability exists in the Toxicity of Global Methicillin-resistant Staphylococcus aureus Lineages.

2021 ◽  
Author(s):  
Maisem Laabei ◽  
Sharon Peacock ◽  
Beth Blane ◽  
Sarah Louise Baines ◽  
Timothy P. Stinear ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Healthcare Setting ◽  
Toxin Production ◽  
Health Concern ◽  
Accessory Gene ◽  
Toxic Activity ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Toxin Regulation ◽  
Reduced Toxicity

Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily toxin driven, leading to the suggestion that hyper-virulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the toxic activity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced toxicity. Interestingly, the majority of isolates that were attenuated in toxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.

scholarly journals Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages

Microbiology ◽  
2021 ◽  
Vol 167 (12) ◽  
Author(s):  
Maisem Laabei ◽  
Sharon J. Peacock ◽  
Beth Blane ◽  
Sarah L. Baines ◽  
Benjamin P. Howden ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Type Species ◽  
Healthcare Setting ◽  
Health Concern ◽  
Accessory Gene ◽  
Methicillin Resistant ◽  
Content Type ◽  
Link Type ◽  
Accessory Gene Regulator ◽  
Toxin Regulation

Staphylococcus aureus is a major human pathogen where the emergence of antibiotic resistant lineages, such as methicillin-resistant S. aureus (MRSA), is a major health concern. While some MRSA lineages are restricted to the healthcare setting, the epidemiology of MRSA is changing globally, with the rise of specific lineages causing disease in healthy people in the community. In the past two decades, community-associated MRSA (CA-MRSA) has emerged as a clinically important and virulent pathogen associated with serious skin and soft-tissue infections (SSTI). These infections are primarily cytotoxin driven, leading to the suggestion that hypervirulent lineages/multi-locus sequence types (STs) exist. To examine this, we compared the cytotoxicity of 475 MRSA isolates representing five major MRSA STs (ST22, ST93, ST8, ST239 and ST36) by employing a monocyte-macrophage THP-1 cell line as a surrogate for measuring gross cytotoxicity. We demonstrate that while certain MRSA STs contain highly toxic isolates, there is such variability within lineages to suggest that this aspect of virulence should not be inferred from the genotype of any given isolate. Furthermore, by interrogating the accessory gene regulator (Agr) sequences in this collection we identified several Agr mutations that were associated with reduced cytotoxicity. Interestingly, the majority of isolates that were attenuated in cytotoxin production contained no mutations in the agr locus, indicating a role of other undefined genes in S. aureus toxin regulation.

scholarly journals Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 804
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Mrna Level ◽  
Accessory Gene ◽  
Biofilm Inhibition ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Release Assay ◽  
Necrosis Factor

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen of nosocomial infection, which is resistant to most antibiotics. Presently, anti-virulence therapy and anti-biofilm therapy are considered to be promising alternatives. In the current work, we investigated the influence of bisdemethoxycurcumin (BDMC) on the virulence-related exoproteins and the biofilm formation using a reference strain and clinic isolated strains. Western blotting, quantitative RT-PCR, and tumor necrosis factor (TNF) release assay were performed to assess the efficacy of BDMC in reducing the expression of Staphylococcus enterotoxin-related exoproteins (enterotoxin A, enterotoxin B) and α-toxin in MRSA. The anti-biofilm activity of BDMC was evaluated through a biofilm inhibition assay. The study suggests that sub-inhibitory concentrations of BDMC significantly inhibited the expression of sea, seb, and hla at the mRNA level in MRSA. Moreover, the expression of virulence-related exoproteins was significantly decreased by down-regulating accessory gene regulator agr, and the inhibition of biofilms formation was demonstrated by BDMC at sub-inhibitory concentrations. Consequently, the study suggests that BDMC may be a potential natural antibacterial agent to release the pressure brought by antibiotic resistance.

scholarly journals Population Studies of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide

2000 ◽  
Vol 182 (20) ◽  
pp. 5721-5729 ◽  
Author(s):  
Willem van Leeuwen ◽  
Wendy van Nieuwenhuizen ◽  
Christel Gijzen ◽  
Henri Verbrugh ◽  
Alex van Belkum
Keyword(s):  
Staphylococcus Aureus ◽  
Accessory Gene ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Colonization Dynamics ◽  
Group 2 ◽  
Bacterial Interference ◽  
Different Levels ◽  
Group 1

ABSTRACT The virulence of Staphylococcus aureus is controlled by the accessory gene regulator (agr) system, including an extracellular inducer encoded by agrD. Variableagr PCR restriction fragment length polymorphism (RFLP) patterns of unique S. aureus strains (n = 192) were determined for a region comprising agrD and parts of the neighboring agrC and agrB genes. Twelve unique RFLP patterns were identified among S. aureusstrains in general; these patterns were further specified by sequencing. All sequences could be catalogued in the three currentagr groups. A major proportion of the S. aureusstrains belong to agr group 1, whereas only 6% of the methicillin-susceptible S. aureus strains and 5% of the methicillin-resistant S. aureus strains belong toagr groups 2 and 3, respectively. The homology between groups varied from 75 to 80%, and within groups it varied from 96 to 100%. Different levels of sequence variability were observed in the different agr genes. agr-related bacterial interference among colonizing S. aureus strains in the noses of persistent and intermittent human carriers was studied.S. aureus strains belonging to different agr groups were encountered in the same individual. This may suggest that the activity of the agrD gene product does not define colonization dynamics, which is further substantiated by the rarity ofagr group 2 and 3 strains.

scholarly journals Microbiological and Genotypic Analysis of Methicillin-Resistant Staphylococcus aureus Bacteremia

2008 ◽  
Vol 52 (9) ◽  
pp. 3441-3443 ◽  
Author(s):  
Carlo McCalla ◽  
Davida S. Smyth ◽  
D. Ashley Robinson ◽  
Judith Steenbergen ◽  
Steven A. Luperchio ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Study ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Accessory Gene ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Staphylococcus Aureus Bacteremia ◽  
Genotypic Analysis ◽  
Vancomycin Mics ◽  
Vancomycin Treatment

ABSTRACT In a recent landmark trial of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) isolates, vancomycin MICs were ≥1 μg/ml for only 16% of the isolates, and accessory gene regulator (agr) function as measured by delta-hemolysin activity was absent or reduced in only 28.1% of the isolates. This clinical study did not capture a population of MRSA isolates predictive of vancomycin treatment failure.

scholarly journals Bacterial Targets of Antibiotics in Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 398
Author(s):  
Harshad Lade ◽  
Jae-Seok Kim
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Teichoic Acid ◽  
Acid Synthesis ◽  
Accessory Gene ◽  
Methicillin Resistant ◽  
Accessory Gene Regulator ◽  
Healthcare Settings ◽  
Lipid Ii ◽  
Novel Therapeutic Strategies

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent bacterial pathogens and continues to be a leading cause of morbidity and mortality worldwide. MRSA is a commensal bacterium in humans and is transmitted in both community and healthcare settings. Successful treatment remains a challenge, and a search for new targets of antibiotics is required to ensure that MRSA infections can be effectively treated in the future. Most antibiotics in clinical use selectively target one or more biochemical processes essential for S. aureus viability, e.g., cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), or metabolic processes, such as folic acid synthesis. In this review, we briefly describe the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in S. aureus. Further, several components of bacterial cellular processes, such as teichoic acid, aminoacyl-tRNA synthetases, the lipid II cycle, auxiliary factors of β-lactam resistance, two-component systems, and the accessory gene regulator quorum sensing system, are discussed as promising targets for novel antibiotics. A greater molecular understanding of the bacterial targets of antibiotics has the potential to reveal novel therapeutic strategies or identify agents against antibiotic-resistant pathogens.

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