Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance DOI Open Access
Erik Larsen, R. Jeremy Johnson

Drug Development Research, Journal Year: 2018, Volume and Issue: 80(1), P. 33 - 47

Published: Oct. 10, 2018

Abstract The rise of antibiotic resistance necessitates the search for new platforms drug development. Prodrugs are common tools overcoming drawbacks typically associated with formulation and delivery, ester prodrugs providing a classic strategy masking polar alcohol carboxylic acid functionalities improving cell permeability. Ester normally designed to have simple groups, as they expected be cleaved reactivated by wide spectrum cellular esterases. However, number pathogenic commensal microbial esterases been found possess significant substrate specificity can play an unexpected role in metabolism. protection also introduce antimicrobial properties into previously nontoxic drugs through alterations permeability or solubility. Finally, mutation is novel mechanism development resistance. In this review, we highlight important xenobiotic functions discuss application targeting infections combating Esterases often overlooked therapeutic targets. Yet, growing need develop antibiotics, thorough understanding function their combined action prodrug antibiotics will support design future therapeutics.

Language: Английский

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options DOI Creative Commons

Chang-Ro Lee,

Jung Hun Lee,

Moonhee Park

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2017, Volume and Issue: 7

Published: March 13, 2017

Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in modern healthcare system. Due to prevalence and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective treating this pathogen. To overcome problem, knowledge pathogenesis antibiotic resistance mechanisms important. In review, we summarize current studies on virulence factors that contribute pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, protein secretion systems. Mechanisms organism, acquirement -lactamases, up-regulation multidrug efflux pumps, modification aminoglycosides, permeability defects, alteration target sites, also discussed. Lastly, novel prospective treatment options summarized.

Language: Английский

Citations

860
Staphylococcus aureus Toxins and Their Molecular Activity in Infectious Diseases DOI Creative Commons
Diana Oliveira, Anabela Borges, Manuel Simões

et al.

Toxins, Journal Year: 2018, Volume and Issue: 10(6), P. 252 - 252

Published: June 19, 2018

Staphylococcus aureus is a microorganism resident in the skin and nasal membranes with dreadful pathogenic potential to cause variety of community hospital-acquired infections. The frequency these infections increasing their treatment becoming more difficult. ability S. form biofilms emergence multidrug-resistant strains are main reasons determining challenge dealing aureus' infectious capacity its success as pathogen related expression virulence factors, among which production wide toxins highlighted. For this reason, better understanding needed enable development new strategies reduce consequently improve therapeutic approaches. This review focuses on toxin-based pathogenesis role diseases.

Language: Английский

Citations

435
Staphylococcus aureusSecreted Toxins and Extracellular Enzymes DOI
Kayan Tam, Victor J. Torres

Microbiology Spectrum, Journal Year: 2019, Volume and Issue: 7(2)

Published: March 15, 2019

is a formidable pathogen capable of causing infections in different sites the body variety vertebrate animals, including humans and livestock. A major contribution to success

Language: Английский

Citations

324
Plasma membrane integrity: implications for health and disease DOI Creative Commons
Dustin A. Ammendolia, William M. Bement, John H. Brumell

et al.

BMC Biology, Journal Year: 2021, Volume and Issue: 19(1)

Published: April 13, 2021

Abstract Plasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma damage from a multitude of stressors in the extra- and intra-cellular environment. To avoid lethal consequences, are equipped with repair pathways to restore integrity. Here, we assess whole-body perspective. We highlight role tissue-specific health disease examine across diverse cell types. Furthermore, outline impact genetic environmental factors on how these contribute pathogenesis different tissues.

Language: Английский

Citations

161
Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides DOI Creative Commons
Yue Zheng, Rachelle L. Hunt,

Amer E. Villaruz

et al.

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(3), P. 301 - 313.e9

Published: Feb. 4, 2022

Language: Английский

Citations

159
A systematic review of natural products for skin applications: Targeting inflammation, wound healing, and photo-aging DOI Creative Commons
Andreia S. Fernandes, Pedro Rodrigues, Manuela Pintado

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 115, P. 154824 - 154824

Published: April 19, 2023

Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When cells are incapable maintain balance between antioxidant defenses and reactive oxygen species, no longer can keep its integrity homeostasis. Chronic inflammation, premature aging, tissue damage, immunosuppression possible consequences induced by sustained exposure environmental endogenous species. Skin immune non-immune together with microbiome essential efficiently trigger responses For this reason, an ever-increasing demand for novel molecules capable of modulating functions in has risen level their development, particularly field natural product-derived molecules. In review, we explore different classes showed evidence modulate responses, as well target receptors signaling pathways. Moreover, describe role polyphenols, polysaccharides, fatty acids, peptides, probiotics treatments conditions, including wound healing, infection, allergies, aging. Literature was searched, analyzed, collected using databases, PubMed, Science Direct, Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., combinations these keywords. Natural products offer solutions conditions. Significant anti-inflammatory activities were reported, followed ability skin. Several membrane-bound recognize diverse types natural-derived molecules, promoting improve Despite increasing progress drug discovery, limiting need future clarification. Understanding safety, biological activities, precise mechanisms action a priority characterization active compounds responsible that. This review provides directions studies development new important pharmaceutical cosmeceutical value.

Language: Английский

Citations

106
Acinetobacter baumannii in the critically ill: complex infections get complicated DOI Creative Commons
Ilaria Cavallo, Alessandra Oliva,

Rebecca Pages

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 22, 2023

is increasingly associated with various epidemics, representing a serious concern due to the broad level of antimicrobial resistance and clinical manifestations. During last decades,

Language: Английский

Citations

57
Principles of Infectious Diseases DOI
Ranish Shrestha, Sunil Shrestha, Asmita Priyadarshini Khatiwada

et al.

Springer eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 25

Published: Jan. 1, 2023

Language: Английский

Citations

33
Membrane damage and repair: a thin line between life and death DOI Creative Commons
Caroline Barisch, Joost C. M. Holthuis, Katia Cosentino

et al.

Biological Chemistry, Journal Year: 2023, Volume and Issue: 404(5), P. 467 - 490

Published: Feb. 22, 2023

Abstract Bilayered membranes separate cells from their surroundings and form boundaries between intracellular organelles the cytosol. Gated transport of solutes across enables to establish vital ion gradients a sophisticated metabolic network. However, an advanced compartmentalization biochemical reactions makes also particularly vulnerable membrane damage inflicted by pathogens, chemicals, inflammatory responses or mechanical stress. To avoid potentially lethal consequences injuries, continuously monitor structural integrity readily activate appropriate pathways plug, patch, engulf shed damaged area. Here, we review recent insights into cellular mechanisms that underly effective maintenance integrity. We discuss how respond lesions caused bacterial toxins endogenous pore-forming proteins, with primary focus on intimate crosstalk proteins lipids during wound formation, detection elimination. delicate balance repair determines cell fate upon infection activation pro-inflammatory death pathways.

Language: Английский

Citations

30
Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase DOI Creative Commons
Chongyang Wang, Changshui Liu,

Xiaochuan Zhu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 9, 2023

Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic using a single active site. This interesting phenomenon widely distributed in catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of promiscuity very limited. Herein, we report structural mechanism underlying substrate catalytic Vibrio dual lipase/transferase (VDLT). Crystal structures VDLT from alginolyticus (ValDLT) its fatty acid complexes were solved, revealing prominent flexibility. In particular, "Ser-His-Asp" triad machinery ValDLT contains an intrinsically flexible oxyanion hole. Analysis ligand-bound mutagenesis showed that hole other binding residues undergo distinct conformational changes to facilitate promiscuity. Our study reveals previously unknown form famous proposes "catalytic site tuning" expand paradigm

Language: Английский

Citations

24