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Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis
(2024)
William R Miller
;
April Nguyen
;
Kavindra V Singh
;
Samie Rizvi
;
Ayesha Khan
<jats:title>Abstract</jats:title> <jats:p>Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.</jats:p>
Scopus© Citations 2 3
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Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocáceas gram positivas
(2012)
ARAOS BRALIC, RAFAEL IGNACIO
;
Patricia García
;
Leonardo Chanqueo
;
Jaime Labarca
21Scopus© Citations 5
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Multisite Detection of Tn
1549
-Mediated
vanB
Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida
(2023)
Shelby R. Simar
;
Truc T. Tran
;
Kirsten B. Rydell
;
Diana Panesso
;
German A. Contreras
<jats:p> In the United States, <jats:italic>vanB</jats:italic> -mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant <jats:named-content content-type="genus-species">Enterococcus faecalis</jats:named-content> isolates causing bacteremia in unique patients in spatiotemporally distinct settings. </jats:p>
7 1Scopus© Citations 3
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A liaR Deletion Restores Susceptibility to Daptomycin and Antimicrobial Peptides in Multidrug-Resistant Enterococcus faecalis
(2014)
Jinnethe Reyes
;
Diana Panesso
;
Truc T. Tran
;
Nagendra N. Mishra
;
Melissa R. Cruz
7 1Scopus© Citations 82
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Antimicrobial Susceptibility Testing for Enterococci
(2022)
Ayesha Khan
;
William R. Miller
;
Dierdre Axell-House
;
MUNITA SEPULVEDA, JOSE MANUEL
;
Cesar A. Arias
<jats:p>Enterococci are major, recalcitrant nosocomial pathogens with a wide repertoire of intrinsic and acquired resistance determinants and the potential of developing resistance to all clinically available antimicrobials. As such, multidrug-resistant enterococci are considered a serious public health threat.</jats:p>
1Scopus© Citations 57 1
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New Perspectives on Antimicrobial Agents: Long-Acting Lipoglycopeptides
(2022)
Truc T. Tran
;
Sara Gomez Villegas
;
Samuel L. Aitken
;
Susan M. Butler-Wu
;
Alex Soriano
<jats:p>The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections.</jats:p>
5Scopus© Citations 29
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Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I)
(2021)
German A Contreras
;
MUNITA SEPULVEDA, JOSE MANUEL
;
Shelby Simar
;
Courtney Luterbach
;
An Q Dinh
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.</jats:p> </jats:sec>
5Scopus© Citations 42
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Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America
(2020)
Betsy E Castro
;
Maritza Berrio
;
Monica L Vargas
;
Lina P Carvajal
;
Lina V Millan
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and 2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14→Ile (90%) and VraT Glu-156→Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.</jats:p></jats:sec>
3 1Scopus© Citations 14
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Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections
(2019)
German A. Contreras
;
MUNITA SEPULVEDA, JOSE MANUEL
;
Cesar A. Arias
1Scopus© Citations 36
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Resistencia a antibióticos de última línea en cocos Gram positivos: la era posterior a la vancomicina
(2014)
Sandra Rincón
;
Diana Panesso
;
Lorena Díaz
;
Lina P. Carvajal
;
Jinnethe Reyes
Scopus© Citations 30 1

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