is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF ) is described as a new determinant of virulence in , using the infection model . The gene was found to be required for the ability to kill . The transporter encoded by this gene is also necessary for antimicrobial peptide (AMP) resistance, specifically against histatin-5. Interestingly, AMP expression was found to be strongly activated in response to infection, suggesting AMPs are a key antifungal defense. CgTpo4 was also found to be a plasma membrane exporter of polyamines, especially spermidine, suggesting that CgTpo4 is able to export polyamines and AMPs, thus conferring resistance to both stress agents. Altogether, this study presents the polyamine exporter CgTpo4 as a determinant of virulence, which acts by protecting the yeast cells from the overexpression of AMPs, deployed as a host defense mechanism.
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http://dx.doi.org/10.3390/ijms22031376 | DOI Listing |
PLoS Negl Trop Dis
January 2025
Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Background: The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is known for its capacity to cause severe neurological disease in Asia. Neurotropic flaviviruses within the Japanese encephalitis (JE) serogroup possess the distinctive feature of expressing a unique nonstructural protein, NS1'. The NS1' protein consists of the full NS1 protein with an additional 52 amino acid extension at the C-terminus and has been demonstrated to exhibit virulence in mammalian hosts upon infection.
View Article and Find Full Text PDFJADA Found Sci
October 2024
Division of Biomaterial and Biomedical Sciences, Department of Oral Rehabilitation and Biosciences, School of Dentistry, Oregon Health & Science University, Portland, OR.
The longevity of direct esthetic restorations is severely compromised because of, among other things, a loss of function that comes from their susceptibility to biofilm-mediated secondary caries, with being the most prevalent associated pathogen. Strategies to combat biofilms range from dental compounds that can disrupt multispecies biofilms in the oral cavity to approaches that specifically target caries-causing bacteria such as . One strategy is to include those antibacterial compounds directly in the material so they can be available long-term in the oral cavity and localized at the margin of the restorations, in which many of the failures initiate.
View Article and Find Full Text PDFACS Omega
January 2025
Infectious Diseases Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir 180001, India.
The insertion of β-amino acids and replacement of the amide bond with a urea bond in antimicrobial peptide sequences are promising approaches to enhance the antibacterial activity and improve proteolytic stability. Herein, we describe the synthesis, characterization, and antibacterial activity of short αβ cationic hybrid peptides LA-Orn-βAcc-PEA, ; LA-Lys-βAcc-PEA, ; and LA-Arg-βAcc-PEA, in which a C12 lipid chain is conjugated at the N terminus of peptide through urea bonds. Further, we evaluated all the peptides against both and methicillin-resistant (MRSA) and their multidrug resistant (MDR) clinical isolates.
View Article and Find Full Text PDFProtein Sci
February 2025
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.
View Article and Find Full Text PDFFolia Microbiol (Praha)
January 2025
Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, 211012, Uttar Pradesh, India.
Bacterial biofilms exhibit remarkable resistance against conventional antibiotics and are capable of evading the humoral immune response. They account for nearly 80% of chronic infections in humans. Development of bacterial biofilms on medical implants results in their malfunctioning and subsequently leads to high mortality rates worldwide.
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