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

Novel Antimicrobial Approaches to Combat Bacterial Biofilms Associated with Urinary Tract Infections DOI Creative Commons
Giuseppe Mancuso,

Marilena Trinchera,

Angelina Midiri

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(2), P. 154 - 154

Published: Feb. 4, 2024

Urinary tract infections (UTIs) are prevalent bacterial in both community and healthcare settings. They account for approximately 40% of all require around 15% antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs several decades, the significant increase resistance recent years has made many previously effective treatments ineffective. Biofilm on medical equipment settings creates a reservoir pathogens that can easily be transmitted patients. catheter frequently observed hospitals caused by microbes form biofilm after is inserted into bladder. Managing biofilms challenging due emergence resistance. Biofilms enable evade host’s innate immune defences, resulting long-term persistence. The incidence sepsis spread bloodstream increasing, drug-resistant may even more prevalent. While availability upcoming tests identify cause infection its spectrum critical, it alone will not solve problem; innovative treatment approaches also needed. This review analyses main characteristics formation drug recurrent uropathogen-induced UTIs. importance alternative therapies combatting biofilm-caused UTI emphasised.

Language: Английский

Citations

10
Treatment and Management of Acinetobacter Pneumonia: Lessons Learned from Recent World Event DOI Creative Commons
Karyne Rangel, Salvatore G. De-Simone

Infection and Drug Resistance, Journal Year: 2024, Volume and Issue: Volume 17, P. 507 - 529

Published: Feb. 1, 2024

Abstract: Acinetobacter pneumonia is a significant healthcare-associated infection that poses considerable challenge to clinicians due its multidrug-resistant nature. Recent world events, such as the COVID-19 pandemic, have highlighted need for effective treatment and management strategies pneumonia. In this review, we discuss lessons learned from recent particularly in context of We performed an extensive literature review uncover studies information pertinent topic. The pandemic underscored importance control measures healthcare settings, including proper hand hygiene, isolation protocols, personal protective equipment use, prevent spread pathogens like . Additionally, crucial role antimicrobial stewardship programs optimizing antibiotic use curbing emergence resistance. Advances diagnostic techniques, rapid molecular testing, also proven valuable identifying infections promptly. Furthermore, limited availability antibiotics treating caused A. baumannii , alternative are needed peptides, bacteriophages their enzymes, nanoparticles, photodynamic chelate therapy. provided insights into These emphasize significance control, stewardship, early diagnostics combating challenging infection. Keywords: ventilator-associated pneumonia, VAP, hospital-acquired HAP, carbapenem-resistant CRAB,

Language: Английский

Citations

10
Clinical and Biological Features of Cutibacterium (Formerly Propionibacterium)avidum, an Underrecognized Microorganism DOI Open Access
Stéphane Corvec

Clinical Microbiology Reviews, Journal Year: 2018, Volume and Issue: 31(3)

Published: May 29, 2018

The recent description of the genus

Language: Английский

Citations

81
Industrial uses of phospholipases: current state and future applications DOI
Sebastián Cerminati,

Luciana Paoletti,

Andrés Aguirre

et al.

Applied Microbiology and Biotechnology, Journal Year: 2019, Volume and Issue: 103(6), P. 2571 - 2582

Published: Feb. 7, 2019

Language: Английский

Citations

64
The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis DOI Creative Commons
Johanna Rohrhofer, Benjamin Zwirzitz, Evelyne Selberherr

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 14, 2021

The large surfaces of gastrointestinal (GI) organs are well adapted to their diverse tasks selective nutritional uptake and defense against the external environment. To maintain a functional balance, vast number immune cells is located within mucosa. A strictly regulated response required impede constant inflammation barrier function. An increasing prevalence GI diseases has been reported in Western societies over past decades. This surge disorders linked dietary changes followed by an imbalance gut microbiome, leading chronic, low grade epithelium. counteract health care costs associated with diseases, it paramount understand mechanisms driving immuno-nutrition, associations between compounds, commensal microbiota, host response. Dietary compounds such as lipids, play central role Bioactive sphingolipids (SLs), e.g. sphingomyelin (SM), sphingosine (Sph), ceramide (Cer), sphingosine-1- phosphate (S1P) ceramide-1-phosphate (C1P) may derive from SLs ingested through diet. They not only integral components cell membranes, they additionally modulate trafficking precursors for mediators second messenger molecules. By regulating intracellular calcium levels, motility, proliferation apoptosis, SL metabolites have described influence homeostasis positively detrimentally. Furthermore, suggested induce shift microbiota. Modes action range competing bacteria intestinal attachment prevention pathogen invasion innate immediate mechanisms. can also be produced microorganisms, directly impacting metabolic pathways. review aims summarize recent findings on signaling variations SLs. We highlight novel insights impact function, which Knowledge gaps current literature will discussed address questions relevant understanding pivotal define balanced healthy diet disease treatment.

Language: Английский

Citations

44
Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies DOI

Céline Vidaillac,

Sanjay H. Chotirmall

Expert Review of Respiratory Medicine, Journal Year: 2021, Volume and Issue: 15(5), P. 649 - 662

Published: March 19, 2021

Introduction: Bronchiectasis is a chronic endobronchial suppurative disease characterized by irreversibly dilated bronchi damaged repeated polymicrobial infections and predominantly, neutrophilic airway inflammation. Some consider bronchiectasis syndromic consequence of several different causes whilst others view it as an individual entity. In most patients, identifying underlying cause remains challenging. The acquisition colonization affected airways Pseudomonas aeruginosa represent critical adverse clinical for its progression management.Areas covered: this review, we outline pre-clinical peer-reviewed research published in the last 5 years, focusing on pathogenesis role P. virulence shaping host inflammatory immune responses airway. We further detail infection, lung microbiome, address therapeutic options bronchiectasis.Expert opinion:P. represents key pulmonary pathogen that acute and/or infection. Eradication can prevent progression. Novel strategies are emerging include combination-based approaches. Addressing infection caused necessary to damage, loss function exacerbations, all which contribute outcome.

Language: Английский

Citations

42
Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network DOI
Jan Skácel, Barbara S. Slusher, Takashi Tsukamoto

et al.

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 64(1), P. 279 - 297

Published: Jan. 4, 2021

Ceramides are composed of a sphingosine and single fatty acid connected by an amide linkage. As one the major classes biologically active lipids, ceramides their upstream downstream metabolites have been implicated in several pathological conditions including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, inflammation. Consequently, tremendous efforts devoted to deciphering dynamics metabolic pathways involved ceramide biosynthesis. Given that distinct enzymes can produce ceramide, different enzyme targets pursued depending on underlying disease mechanism. The main objective this review is provide comprehensive overview small molecule inhibitors reported date for each these ceramide-producing from medicinal chemistry perspective.

Language: Английский

Citations

41
A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes DOI Creative Commons
Gina M. Borgo, Thomas Burke, Cuong J. Tran

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 27, 2022

Abstract Rickettsia species of the spotted fever group are arthropod-borne obligate intracellular bacteria that can cause mild to severe human disease. These invade host cells, replicate in cell cytosol, and spread from cell. To access cytosol avoid immune detection, they escape membrane-bound vacuoles by expressing factors disrupt membranes. Here, we show a patatin-like phospholipase A2 enzyme (Pat1) facilitates parkeri infection promoting membranes cell-cell spread. Pat1 is important for mouse model and, at cellular level, crucial efficiently escaping single double into avoiding galectins mark damaged also polyubiquitin, preventing recruitment autophagy receptor p62, actin-based motility

Language: Английский

Citations

31
The epidermal lipid barrier in microbiome–skin interaction DOI Open Access
Arnaud Kengmo Tchoupa, Dorothee Kretschmer, Birgit Schittek

et al.

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 31(7), P. 723 - 734

Published: Feb. 22, 2023

Language: Английский

Citations

22
An insight into MDR Acinetobacter baumannii infection and its pathogenesis: Potential therapeutic targets and challenges DOI
Sukriti Singh, Sushmita Singh,

Mala Trivedi

et al.

Microbial Pathogenesis, Journal Year: 2024, Volume and Issue: 192, P. 106674 - 106674

Published: May 5, 2024

Language: Английский

Citations

6