skip to main content

Explore Research Products in the NSF-PAR

Title: Methicillin-Resistant Staphylococcus aureus (MRSA): Antibiotic-Resistance and the Biofilm Phenotype
Staphylococcus aureus (S. aureus) is an asymptomatic colonizer of 30% of all human beings. While generally benign, antibiotic resistance contributes to the success of S. aureus as a human pathogen. Resistance is rapidly evolved through a wide portfolio of mechanisms including horizontal gene transfer and chromosomal mutation. In addition to traditional resistance mechanisms, a special feature of S. aureus pathogenesis is its ability to survive on both biotic and abiotic surfaces in the biofilm state. Due to this characteristic, S. aureus is a leading cause of human infection. Methicillin-resistant S. aureus (MRSA) in particular has emerged as a widespread cause of both community- and hospital-acquired infections. Currently, MRSA is responsible for 10-fold more infections than all multi-drug resistant (MDR) Gram-negative pathogens combined. Recently, MRSA was classified by the World Health Organization (WHO) as one of twelve priority pathogens that threaten human health. In this targeted mini-review, we discuss MRSA biofilm production, the relationship of biofilm production to antibiotic resistance, and front-line techniques to defeat the biofilm-resistance system.  more » « less
Award ID(s):
1847804
NSF-PAR ID:
10088108
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
MedChemComm
ISSN:
2040-2503
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ( , Risk Analysis)
    Abstract

    The World Health Organization has declared antibiotic resistance “one of the biggest threats to global health.” Mounting evidence suggests that antibiotic use in industrial‐scale hog farming is contributing to the spread of antibiotic‐resistantStaphylococcus aureus. To capture available evidence on these risks, we searched peer‐reviewed studies published before June 2017 and conducted a meta‐analysis of these studies’ estimates of the prevalence of swine‐associated, antibiotic‐resistantS. aureusin animals, humans, and the environment. The 166 relevant studies revealed consistent evidence of livestock‐associated methicillin‐resistantS. aureus(MRSA) in hog herds (55.3%) raised with antibiotics. MRSA prevalence was also substantial in slaughterhouse pigs (30.4%), industrial hog operation workers (24.4%), and veterinarians (16.8%). The prevalence of swine‐associated, multidrug‐resistantS. aureus(MDRSA)—with resistance to three or more antibiotics—is not as well documented. Nonetheless, sufficient studies were available to estimate MDRSA pooled prevalence in conventional hog operation workers (15.0%), workers’ household members (13.0%), and community members (5.37%). Evidence also suggests that antibiotic‐resistantS. aureuscan be present in air, soil, water, and household surface samples gathered in or near high‐intensity hog operations. An important caveat is that prevalence estimates for humans reflect colonization, not active infection, and the health risks of colonization remain poorly understood. In addition, these pooled results may not represent risks in specific locations, due to wide geographic variation. Nonetheless, these results underscore the need for additional preventive action to stem the spread of antibiotic‐resistant pathogens from livestock operations and a streamlined reporting system to track this risk.

     
    more » « less
  2. ; ; ; ; ( , Applied and Environmental Microbiology)
    Dozois, Charles M. (Ed.)
    ABSTRACT Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBCs), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al ( , Advanced Science)
    Abstract

    Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug‐resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin‐resistantS. aureus(MRSA) to a broad spectrum of conventional antibiotics via photo‐disassembly of functional membrane microdomains. The photo‐disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore‐targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug‐resistantS. aureusinfections as well as to screen new lead compounds.

     
    more » « less
  4. ; ; ; ; ; ( , Israel Journal of Chemistry)
    Abstract

    Staphylococcus aureusis a ubiquitous bacterium that has become a major threat to human health due to its extensive toxin production and tremendous capacity for antibiotic resistance (e. g., MRSA “superbug” infections). Amid a worsening antibiotic resistance crisis, new strategies to combat this deadly microbe that remove the selective pressure of traditional approaches are in high demand.S. aureusutilizes an accessory gene regulator (agr) quorum sensing network to monitor its local cellular population and trigger a devastating communal attack, like an invading horde, once a threshold cell density has been reached. The role of theagrsystem in a range of disease types is still being unraveled. Herein, we discuss the present‐day biochemical understanding ofagralong with unresolved details, describe its connection to the progression of infection, and review how chemical strategies have been implemented to study and intercept this signaling pathway. This research is illuminating the potential ofagras an anti‐virulence target inS. aureusand should inform the study of similar, yet less studied,agrsystems in related bacterial pathogens.

     
    more » « less
  5. ; ; ; ; ; ; ( , Antibiotics)
    The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant Staphylococcus aureus (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D 1H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email