Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: May 15, 2024

Abstract Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they essential to restrict proliferation of opportunistic pathogens such as Staphylococcus aureus . These (AFAs) elicit bacterial adaptation strategies, which have yet be fully elucidated. Characterizing pervasive mechanisms used by S. resist AFAs could open new avenues prevent pathogen colonization. Here, we identify lipase Lip2 a novel resistance factor against AFAs. detoxifies via esterification cholesterol. This is reminiscent activity acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation rare in blood, nose, strains, suggesting particularly important role host – microbe interactions. mouse model colonization, bacteria were protected from sapienic acid (a human-specific AFA) cholesterol- lipase-dependent manner. results suggest long-sought FAME exquisitely manipulates environmental lipids promote otherwise inhospitable niches.

Language: Английский

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Overcoming Fish Defences: The Virulence Factors of Yersinia ruckeri

Genes, Journal Year: 2019, Volume and Issue: 10(9), P. 700 - 700

Published: Sept. 11, 2019

Yersinia ruckeri is the causative agent of enteric redmouth disease, a bacterial infection marine and freshwater fish. The disease mainly affects salmonids, outbreaks have significant economic impact on fish farms all over world. Vaccination routines are in place against major serotypes Y. but not effective cases. Despite importance detailed molecular understanding lacking. A considerable number mostly omics-based studies been performed recent years to identify genes related virulence. This review summarizes knowledge virulence factors. Understanding pathogenicity will aid developing more efficient vaccines antimicrobial compounds directed disease.

Language: Английский

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Highlights in the knowledge of brown spider toxins

˜The œJournal of venomous animals and toxins including tropical diseases, Journal Year: 2017, Volume and Issue: 23(1)

Published: Feb. 8, 2017

Brown spiders are venomous arthropods that use their venom for predation and defense. In humans, bites of these animals provoke injuries including dermonecrosis with gravitational spread lesions, hematological abnormalities impaired renal function. The signs symptoms observed following a brown spider bite called loxoscelism. is complex mixture toxins enriched in low molecular mass proteins (4-40 kDa). Characterization the confirmed presence three highly expressed protein classes: phospholipases D, metalloproteases (astacins) insecticidal peptides (knottins). Recently, levels expression have also been found Loxosceles venom, such as serine proteases, protease inhibitors (serpins), hyaluronidases, allergen-like histamine-releasing factors. toxin belonging to phospholipase-D family (also known dermonecrotic toxin) most studied class toxins. This single-handedly can induce inflammatory response, dermonecrosis, hemolysis, thrombocytopenia failure. functional role hyaluronidase spreading factor loxoscelism has demonstrated. However, biological characterization other remains unclear mechanism by which exert noxious effects yet be fully elucidated. aim this review provide an insight into toxicology, description historical data already available literature. article, identification processes novel biology proteomic approaches, structural based on x-ray crystallography putative biotechnological uses described along future perspectives field.

Language: Английский

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Macrophage–Bacteria Interactions—A Lipid-Centric Relationship

Frontiers in Immunology, Journal Year: 2017, Volume and Issue: 8

Published: Dec. 20, 2017

Macrophages are professional phagocytes at the front line of immune defenses against foreign bodies and microbial pathogens. Various bacteria, which responsible for deadly diseases including tuberculosis salmonellosis, capable hijacking this important cell type thrive intracellularly, either in cytoplasm or specialized vacuoles. Tight regulation cellular metabolism is critical shaping macrophage polarization states functions. Lipids, besides being bulk component biological membranes, serve as energy sources well signaling molecules during infection inflammation. With advent systems-scale analyses genes, transcripts, proteins metabolites, combination with classical biology, it increasingly evident that macrophages undergo extensive lipid remodeling activation infection. Each bacterium species has evolved its own tactics to manipulate host towards advantage. Furthermore, modulation affects disease susceptibility outcome infections, highlighting roles lipids infectious diseases. Here, we will review emerging complex host-pathogen relationship discuss recent methodologies employed probe these versatile metabolites process. An improved understanding lipid-centric nature infections can lead identification Achilles' heel pathogens host-directed targets therapeutic interventions. Currently, lipid-moderating drugs clinically available a range non-communicable diseases, anticipate potentially be tapped into various infections.

Language: Английский

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Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance

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

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