scholarly journals Penicillin Resistance in Enterococcus faecalis: Molecular Determinants and Epidemiology

2012 ◽  
Vol 61 (3) ◽  
pp. 153-160 ◽  
Author(s):  
IWONA GAWRYSZEWSKA ◽  
WALERIA HRYNIEWICZ ◽  
EWA SADOWY
Keyword(s):  
High Risk ◽  
Enterococcus Faecalis ◽  
Significant Role ◽  
Drug Target ◽  
Penicillin Resistance ◽  
Penicillin Binding Protein ◽  
Hospital Acquired Infections ◽  
Molecular Determinants ◽  
Hospital Acquired ◽  
Near Future

Enterococcus faecalis plays a significant role in hospital-acquired infections (HAIs), and combination of penicillin with aminoglycoside is important in therapy of invasive HAIs. Penicillin resistance in this organism is due to modification of the drug target, penicillin-binding protein (PBP5), its overproduction and expression of β-lactamase. Although rare, this phenotype is often associated with multi-resistant high-risk enterococcal clonal complexes (HiRECCs), such as CC2 and CC9 which may promote its spread in the near future.

scholarly journals The interplay of SARS-CoV-2 and Clostridioides difficile infection

2021 ◽  
Vol 16 (6) ◽  
pp. 439-443
Author(s):  
Sahil Khanna ◽  
Colleen S Kraft
Keyword(s):  
High Risk ◽  
Infection Control ◽  
Gastrointestinal Symptoms ◽  
Control Measures ◽  
Antibiotic Exposure ◽  
Hospital Acquired Infections ◽  
Infection Control Measures ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Hospital Acquired

The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.

scholarly journals Comparative Biofilm Assays Using Enterococcus faecalis OG1RF Identify New Determinants of Biofilm Formation

mBio ◽  
2021 ◽  
Author(s):  
Julia L. E. Willett ◽  
Jennifer L. Dale ◽  
Lucy M. Kwiatkowski ◽  
Jennifer L. Powers ◽  
Michelle L. Korir ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Nutrient Availability ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Growth Conditions ◽  
Complete Understanding ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

E. faecalis is an opportunistic pathogen and a leading cause of hospital-acquired infections, in part due to its ability to form biofilms. A complete understanding of the genes required for E. faecalis biofilm formation as well as specific features of biofilm morphology related to nutrient availability and growth conditions is crucial for understanding how E. faecalis biofilm-associated infections develop and resist treatment in patients.

scholarly journals Antagonistic Donor Density Effect Conserved in Multiple Enterococcal Conjugative Plasmids

2016 ◽  
Vol 82 (15) ◽  
pp. 4537-4545 ◽  
Author(s):  
Arpan Bandyopadhyay ◽  
Sofie O'Brien ◽  
Kristi L. Frank ◽  
Gary M. Dunny ◽  
Wei-Shou Hu
Keyword(s):  
Antibiotic Resistance ◽  
Enterococcus Faecalis ◽  
Virulence Determinants ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Donor Density ◽  
Donor Cells ◽  
Inhibitor Peptide ◽  
Hospital Acquired ◽  
High Donor

ABSTRACTEnterococcus faecalis, a common causative agent of hospital-acquired infections, is resistant to many known antibiotics. Its ability to acquire and transfer resistance genes and virulence determinants through conjugative plasmids poses a serious concern for public health. In some cases, induction of transfer ofE. faecalisplasmids results from peptide pheromones produced by plasmid-free recipient cells, which are sensed by the plasmid-bearing donor cells. These plasmids generally encode an inhibitory peptide that competes with the pheromone and suppresses self-induction of donors. We recently demonstrated that the inhibitor peptide encoded on plasmid pCF10 is part of a unique quorum-sensing system in which it functions as a “self-sensing signal,” reducing the response to the pheromone in a density-dependent fashion. Based on the similarities between regulatory features controlling conjugation in pAD1 and pAM373 and those controlling conjugation in pCF10, we hypothesized that these plasmids are likely to exhibit similar quorum-sensing behaviors. Experimental findings indicate that for both pAD1 and pAM373, high donor densities indeed resulted in decreased induction of the conjugation operon and reduced conjugation frequencies. This effect was restored by the addition of exogenous inhibitor, confirming that the inhibitor serves as an indicator for donor density. Donor density also affects cross-species conjugative plasmid transfer. Based on our experimental results, we propose models for induction and shutdown of the conjugation operon in pAD1 and pAM373.IMPORTANCEEnterococcus faecalisis a leading cause of hospital-acquired infections. Its ability to transfer antibiotic resistance and virulence determinants by sharing its genetic material with other bacteria through direct cell-cell contact via conjugation poses a serious threat. Two antagonistic signaling peptides control the transfer of plasmids pAD1 and pAM373: a peptide pheromone produced by plasmid-free recipients triggers the conjugative transfer in plasmid-containing donors, and an inhibitor peptide encoded on the plasmid and produced by donor cells serves to modulate the donor response in accordance with the relative abundance of donors and recipients. We demonstrate that high donor density reduces the conjugation frequency of both of these plasmids, which is a consequence of increased inhibitor concentration in high-donor-density cultures. While most antibiotic strategies end up selecting resistant strains and disrupting the community balance, manipulating bacterial signaling mechanisms can serve as an alternate strategy to prevent the spread of antibiotic resistance.

scholarly journals The Metal Ion-Dependent Adhesion Site Motif of the Enterococcus faecalis EbpA Pilin Mediates Pilus Function in Catheter-Associated Urinary Tract Infection

mBio ◽  
2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Hailyn V. Nielsen ◽  
Pascale S. Guiton ◽  
Kimberly A. Kline ◽  
Gary C. Port ◽  
Jerome S. Pinkner ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Enterococcus Faecalis ◽  
Molecular Basis ◽  
Metal Ion ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Tract Infections ◽  
Hospital Acquired ◽  
Adhesion Site

ABSTRACT Though the bacterial opportunist Enterococcus faecalis causes a myriad of hospital-acquired infections (HAIs), including catheter-associated urinary tract infections (CAUTIs), little is known about the virulence mechanisms that it employs. However, the endocarditis- and biofilm-associated pilus (Ebp), a member of the sortase-assembled pilus family, was shown to play a role in a mouse model of E. faecalis ascending UTI. The Ebp pilus comprises the major EbpC shaft subunit and the EbpA and EbpB minor subunits. We investigated the biogenesis and function of Ebp pili in an experimental model of CAUTI using a panel of chromosomal pilin deletion mutants. A nonpiliated pilus knockout mutant (EbpABC− strain) was severely attenuated compared to its isogenic parent OG1RF in experimental CAUTI. In contrast, a nonpiliated ebpC deletion mutant (EbpC− strain) behaved similarly to OG1RF in vivo because it expressed EbpA and EbpB. Deletion of the minor pilin gene ebpA or ebpB perturbed pilus biogenesis and led to defects in experimental CAUTI. We discovered that the function of Ebp pili in vivo depended on a predicted metal ion-dependent adhesion site (MIDAS) motif in EbpA’s von Willebrand factor A domain, a common protein domain among the tip subunits of sortase-assembled pili. Thus, this study identified the Ebp pilus as a virulence factor in E. faecalis CAUTI and also defined the molecular basis of this function, critical knowledge for the rational development of targeted therapeutics. IMPORTANCE Catheter-associated urinary tract infections (CAUTIs), one of the most common hospital-acquired infections (HAIs), present considerable treatment challenges for physicians. Inherently resistant to several classes of antibiotics and with a propensity to acquire vancomycin resistance, enterococci are particularly worrisome etiologic agents of CAUTI. A detailed understanding of the molecular basis of Enterococcus faecalis pathogenesis in CAUTI is necessary for the development of preventative and therapeutic strategies. Our results elucidated the importance of the E. faecalis Ebp pilus and its subunits for enterococcal virulence in a mouse model of CAUTI. We further showed that the metal ion-dependent adhesion site (MIDAS) motif in EbpA is necessary for Ebp function in vivo. As this motif occurs in other sortase-assembled pili, our results have implications for the molecular basis of virulence not only in E. faecalis CAUTI but also in additional infections caused by enterococci and other Gram-positive pathogens.

scholarly journals The structure of alanine racemase fromAcinetobacter baumannii

2014 ◽  
Vol 70 (9) ◽  
pp. 1199-1205 ◽  
Author(s):  
Emily Davis ◽  
Emma Scaletti-Hutchinson ◽  
Helen Opel-Reading ◽  
Yoshio Nakatani ◽  
Kurt L. Krause
Keyword(s):  
Drug Target ◽  
Alanine Racemase ◽  
Negative Bacterium ◽  
Design Studies ◽  
Structure Based Drug Design ◽  
Antibiotic Resistant ◽  
Hospital Acquired Infections ◽  
Antibiotic Drug ◽  
Resistant Strains ◽  
Hospital Acquired

Acinetobacter baumanniiis an opportunistic Gram-negative bacterium which is a common cause of hospital-acquired infections. Numerous antibiotic-resistant strains exist, emphasizing the need for the development of new antimicrobials. Alanine racemase (Alr) is a pyridoxal 5′-phosphate dependent enzyme that is responsible for racemization between enantiomers of alanine. As D-alanine is an essential component of the bacterial cell wall, its inhibition is lethal to prokaryotes, making it an excellent antibiotic drug target. The crystal structure ofA. baumanniialanine racemase (AlrAba) from the highly antibiotic-resistant NCTC13302 strain has been solved to 1.9 Å resolution. Comparison of AlrAbawith alanine racemases from closely related bacteria demonstrates a conserved overall fold. The substrate entryway and active site of the enzymes were shown to be highly conserved. The structure of AlrAbawill provide the template required for future structure-based drug-design studies.

scholarly journals Genome Sequence of a Novel Enterococcus faecalis Sequence Type 922 Strain Isolated from a Door Handle in the Intensive Care Unit of a District Hospital in Durban, South Africa

2019 ◽  
Vol 8 (35) ◽  
Author(s):  
Christiana O. Shobo ◽  
Daniel G. Amoako ◽  
Mushal Allam ◽  
Arshad Ismail ◽  
Sabiha Y. Essack ◽  
...  
Keyword(s):  
South Africa ◽  
Intensive Care Unit ◽  
Enterococcus Faecalis ◽  
Genome Sequence ◽  
District Hospital ◽  
Sequence Type ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Defense Systems ◽  
Hospital Acquired

Herein, we highlight the genome sequence of a novel Enterococcus faecalis sequence type 922 (ST922) strain isolated in South Africa. The 3,564,442-bp genome harbored defense systems, a resistome, a virulome, and genetic support, which is of importance to the control of hospital-acquired infections. The genomics of Enterococcus faecalis yields greater understanding into its pathogenesis.

scholarly journals Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Erica C. Keffeler ◽  
Vijayalakshmi S. Iyer ◽  
Srivatsan Parthasarathy ◽  
Matthew M. Ramsey ◽  
Matthew J. Gorman ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Enterococcus Faecalis ◽  
Carbon Metabolism ◽  
Sigma Factor ◽  
Alternative Sigma Factor ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

ABSTRACT The alternative sigma factor σ54 has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ54 is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ54 (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection. IMPORTANCE Hospital-acquired infections account for 2 billion dollars annually in increased health care expenses and cause more than 100,000 deaths in the United States alone. Enterococci are the second leading cause of hospital-acquired infections. They form biofilms at surgical sites and are often associated with infections of the urinary tract following catheterization. Nutrient uptake and growth are key factors that influence their ability to cause disease. Our research identified a large set of genes that illuminate nutrient uptake pathways in enterococci. Perturbation of the metabolic circuit reduces virulence in a rabbit endocarditis model, as well as in catheter-associated urinary tract infection in mice. Targeting metabolic pathways that are important in infection may lead to new treatments against multidrug-resistant enterococcal infections.

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