scholarly journals Impact of agr Functionality on the Outcome of Patients with Methicillin-Susceptible Staphylococcus aureus Bacteremia

2021 ◽  
Author(s):  
Jeong Eun Lee ◽  
Shinwon Lee ◽  
Sohee Park ◽  
Soon O. Lee ◽  
Sun H. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Accessory Gene ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Staphylococcus Aureus Bacteremia ◽  
Mssa Infection

Few studies have examined the association between methicillin-susceptible Staphylococcus aureus (MSSA) infection and accessory gene regulator ( agr ) functionality. We evaluated the association between agr dysfunction and mortality in patients with MSSA bacteremia.

scholarly journals Finding of Agr Phase Variants in Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Vishal Gor ◽  
Aya J. Takemura ◽  
Masami Nishitani ◽  
Masato Higashide ◽  
Veronica Medrano Romero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Phase Variation ◽  
Accessory Gene ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Immune Mediated ◽  
A Minor ◽  
First Time ◽  
Phase Variants

ABSTRACT Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing accessory gene regulator (Agr) system. However, a large proportion of clinical S. aureus isolates are consistently found to have a mutationally inactivated Agr system. These mutants have a survival advantage in the host but are considered irreversible mutants. Here we show, for the first time, that a fraction of Agr-negative mutants can revert their Agr activity. By serially passaging Agr-negative strains and screening for phenotypic reversion of hemolysis and subsequent sequencing, we identified two mutational events responsible for reversion: a genetic duplication plus inversion event and a poly(A) tract alteration. Additionally, we demonstrate that one clinical Agr-negative methicillin-resistant S. aureus (MRSA) isolate could reproducibly generate Agr-revertant colonies with a poly(A) tract genetic mechanism. We also show that these revertants activate their Agr system upon phagocytosis. We propose a model in which a minor fraction of Agr-negative S. aureus strains are phase variants that can revert their Agr activity and may act as a cryptic insurance strategy against host-mediated stress. IMPORTANCE Staphylococcus aureus is responsible for a broad range of infections. This pathogen has a vast arsenal of virulence factors at its disposal, but avirulent strains are frequently isolated as the cause of clinical infections. These isolates have a mutated agr locus and have been believed to have no evolutionary future. Here we show that a fraction of Agr-negative strains can repair their mutated agr locus with mechanisms resembling phase variation. The agr revertants sustain an Agr OFF state as long as they exist as a minority but can activate their Agr system upon phagocytosis. These revertant cells might function as a cryptic insurance strategy to survive immune-mediated host stress that arises during infection.

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

2014 ◽  
Vol 22 (12) ◽  
pp. 676-685 ◽  
Author(s):  
Kimberley L. Painter ◽  
Aishwarya Krishna ◽  
Sivaramesh Wigneshweraraj ◽  
Andrew M. Edwards
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Accessory Gene ◽  
Accessory Gene Regulator ◽  
Staphylococcus Aureus Bacteremia

scholarly journals Contribution of Lactococcus lactis Reducing Properties to the Downregulation of a Major Virulence Regulator in Staphylococcus aureus, theagrSystem

2014 ◽  
Vol 80 (22) ◽  
pp. 7028-7035 ◽  
Author(s):  
Sébastien Nouaille ◽  
Lucie Rault ◽  
Sophie Jeanson ◽  
Pascal Loubière ◽  
Yves Le Loir ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Lactic Acid ◽  
Lactococcus Lactis ◽  
Response Regulator ◽  
Food Poisoning ◽  
Accessory Gene ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Virulence Regulator ◽  
Reducing Properties

ABSTRACTStaphylococcus aureusis a major cause of food poisoning outbreaks associated with dairy products, because of the ingestion of preformed enterotoxins. The biocontrol ofS. aureususing lactic acid bacteria (LAB) offers a promising opportunity to fight this pathogen while respecting the product ecosystem. We had previously established the ability ofLactococcus lactis, a lactic acid bacterium widely used in the dairy industry, to downregulate a major staphylococcal virulence regulator, the accessory gene regulator (agr) system, and, as a consequence,agr-controlled enterotoxins. In the present paper, we have shown that the oxygen-independent reducing properties ofL. lactiscontribute toagrdownregulation. Neutralizing lactococcal reduction by adding potassium ferricyanide or maintaining the oxygen pressure constant at 50% releasedagrdownregulation in the presence ofL. lactis. This downregulation still occurred in anS. aureus srrAmutant, indicating that the staphylococcal respiratory response regulator SrrAB was not the only component in the signaling pathway. Therefore, this study clearly demonstrates the ability ofL. lactisreducing properties to interfere with the expression ofS. aureusvirulence, thus highlighting this general property of LAB as a lever to control the virulence expression of this major pathogen in a food context and beyond.

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 Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus Bloodstream Isolates from South Korean Patients

2012 ◽  
Vol 57 (3) ◽  
pp. 1509-1512 ◽  
Author(s):  
Yong Pil Chong ◽  
Eun Sil Kim ◽  
Su-Jin Park ◽  
Ki-Ho Park ◽  
Tark Kim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care ◽  
Hospital Setting ◽  
Care Hospital ◽  
Accessory Gene ◽  
Content Type ◽  
South Korean ◽  
Accessory Gene Regulator ◽  
Clonal Spread ◽  
Hospital Acquired

ABSTRACTWe describe the genetic and microbiological characteristics of methicillin-resistantStaphylococcus aureus(MRSA) bloodstream isolates withagrdysfunction from a tertiary-care hospital in Korea. Of these, ST5-SCCmectype II-agrgroup II MRSA isolates, which are known to be prevalent in hospital-acquired infections in Korea, were the most abundant, because of the clonal spread of a specificagr-defective lineage. This finding suggests that the loss ofagrfunction may confer a potential advantage in a hospital setting. Clonal spread of a specific defective-agrstrain was not observed among community-associated MRSA or methicillin-susceptibleS. aureusclones, regardless of community or hospital acquisition of infection.agr-defective clones, including ST5 and ST239 MRSA, were enriched for heteroresistant vancomycin-intermediateS. aureus.

scholarly journals Front-Loaded Linezolid Regimens Result in Increased Killing and Suppression of the Accessory Gene Regulator System of Staphylococcus aureus

2012 ◽  
Vol 56 (7) ◽  
pp. 3712-3719 ◽  
Author(s):  
Brian T. Tsuji ◽  
Tanya Brown ◽  
Ridhi Parasrampuria ◽  
Daniel A. Brazeau ◽  
Alan Forrest ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Growth Control ◽  
Study Endpoint ◽  
Infection Model ◽  
Accessory Gene ◽  
Bacterial Killing ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Pharmacodynamic Profile ◽  
The Impact

ABSTRACTFront loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded byagr) in methicillin-resistantStaphylococcus aureus(MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 106CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log10CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of −6.15 and −6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a <1.27× increase in the fractional decreases in platelets for all front-loaded regimens versus the 600 mg q12h regimen, except for the highest-dose front-loaded regimen. Front-loading strategies for linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary.

scholarly journals Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
J. Chase McNeil ◽  
Lauren M. Sommer ◽  
Mary Boyle ◽  
Patrick Hogan ◽  
Jesus G. Vallejo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Chronic Osteomyelitis ◽  
Source Control ◽  
Accessory Gene ◽  
Content Type ◽  
Accessory Gene Regulator ◽  
Definitive Therapy ◽  
Inoculum Effect ◽  
Antibiotic Failure ◽  
Ongoing Surveillance

ABSTRACT Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce β-lactamases with affinity for first-generation cephalosporins (1GCs). In the setting of a high inoculum, these β-lactamases may promote the cleavage of 1GCs, a phenomenon known as the cefazolin inoculum effect (CzIE). We evaluated the prevalence and impact of CzIE on clinical outcomes among MSSA acute hematogenous osteomyelitis (AHO) cases. MSSA AHO isolates obtained from two children’s hospitals between January 2011 and December 2018 were procured through ongoing surveillance studies. Isolates were tested for CzIE via a broth macrodilution assay using an inoculum of 107 CFU/ml; CzIE was defined as a cefazolin MIC of ≥16 μg/ml. Isolates were characterized by accessory gene regulator group (agr). The progression from acute to chronic osteomyelitis was considered an important outcome. A total of 250 cases with viable isolates were included. Notably, 14.4% of isolates exhibited CzIE with no observed temporal trend; and 4% and 76% of patients received a 1GC as an empirical and definitive therapy, respectively. CzIE isolates were more often resistant to clindamycin, belonged to agrIII, and associated with the development of chronic osteomyelitis. In multivariable analyses, agrIII, multiple surgical debridements, delayed source control, and CzIE were independently associated with progression to chronic osteomyelitis. A higher rate of chronic osteomyelitis was observed with CzIE isolates regardless of definitive antibiotic choice. CzIE is exhibited by 14.4% of MSSA AHO isolates in children. CzIE is independently associated with progression to chronic osteomyelitis in cases of AHO irrespective of final antibiotic choice. These data suggest that negative outcomes reported with CzIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure.

scholarly journals Virulence and Resistance Determinants of German Staphylococcus aureus ST398 Isolates from Nonhuman Sources

2011 ◽  
Vol 77 (9) ◽  
pp. 3052-3060 ◽  
Author(s):  
M. A. Argudín ◽  
B.-A. Tenhagen ◽  
A. Fetsch ◽  
J. Sachsenröder ◽  
A. Käsbohrer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Virulence Gene ◽  
Diffusion Method ◽  
Accessory Gene ◽  
Disk Diffusion Method ◽  
Content Type ◽  
Resistance Determinants ◽  
Accessory Gene Regulator ◽  
Antimicrobial Resistance Genes

ABSTRACTA series of 100Staphylococcus aureusisolates ascribed to sequence type 398 (ST398) and recovered from different sources (healthy carrier and diseased pigs, dust from pig farms, milk, and meat) in Germany were investigated for their virulence and antimicrobial resistance genetic background. Antimicrobial resistance was determined by the disk diffusion method. Virulence and resistance determinants (37 and 31 genes, respectively) were tested by PCR. Only two virulence profiles, including the accessory gene regulatoragrIand three or four hemolysin-encoding genes, were detected. In contrast, 33 resistance profiles were distinguished (only 11 were shown by more than one isolate). Fifty-nine isolates were multiresistant (four or more antimicrobial classes), and 98 were methicillin resistant (mecApositive). All of the ST398 isolates showed resistance to tetracycline [encoded bytet(M) alone or together withtet(K) and/ortet(L)]. In addition, 98% were resistant to other antimicrobials, including macrolide-lincosamine-streptogramin B (70%, encoded byermA,ermB, andermC, alone or in combination), trimethoprim (65%, mostly due todfrKanddfrG), kanamycin and gentamicin [29% and 14%, respectively, mainly related toaac(6′)-Ie-aph(2″)-Iaand/orant(4′)-Iabut also toaph(3′)-IIIa], chloramphenicol (9%,fexAorcfr), quinupristin-dalfopristin (9%), ciprofloxacin (8%), and trimethoprim-sulfamethoxazole (4%). The heterogeneity of the resistance profiles underlines the ability of the ST398 clone to acquire multiple antimicrobial resistance genes. However, the virulence gene content of the tested isolates was low. Continuous surveillance is needed to clarify whether its pathogenicity potential for animals and humans will increase over time.

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.

Sign in / Sign up

Export Citation Format

Share Document