Percorrer por autor "Manageiro, Vera"
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- Antimicrobial activity of prophage endolysins against critical Enterobacteriaceae antibiotic-resistant bacteriaPublication . Gonçalves, Tiago; Marques, Andreia T.; Manageiro, Vera; Tanoeiro, Luís; Vital, Joana S.; Duarte, Aida; Vítor, Jorge M. B.; Caniça, Manuela; Gaspar, Maria Manuela; Vale, Filipa F.Enterobacteriaceae species are part of the 2017 World Health Organization antibiotic-resistant priority pathogens list for development of novel medicines. Multidrug-resistant Klebsiella pneumoniae is an increasing threat to public health and has become a relevant human pathogen involved in life-threatening infections. Phage therapy involves the use of phages or their lytic endolysins as bioagents for the treatment of bacterial infectious diseases. Gram-negative bacteria have an outer membrane, making difficult the access of endolysins to the peptidoglycan. Here, three endolysins from prophages infecting three distinct Enterobacterales species, Kp2948-Lys from K. pneumoniae, Ps3418-Lys from Providencia stuartii, and Kaer26608-Lys from Klebsiella aerogenes, were purified and exhibited antibacterial activity against their specific bacterium species verified by zymogram assays. These three endolysins were successfully associated to liposomes composed of dimyristoyl phosphatidyl choline (DMPC), dioleoyl phosphatidyl ethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS) at a molar ratio (4:4:2), with an encapsulation efficiency ranging from 24 to 27%. Endolysins encapsulated in liposomes resulted in higher antibacterial activity compared to the respective endolysin in the free form, suggesting that the liposome-mediated delivery system enhances fusion with outer membrane and delivery of endolysins to the target peptidoglycan. Obtained results suggest that Kp2948-Lys appears to be specific for K. pneumoniae, while Ps3418-Lys and Kaer26608-Lys appear to have a broader antibacterial spectrum. Endolysins incorporated in liposomes constitute a promising weapon, applicable in the several dimensions (human, animals and environment) of the One Health approach, against multidrug-resistant Enterobacteriaceae.
- Identifying phage Lysins through genomic analysis of prophages from Acinetobacter baumanniiPublication . Raposo, Maria Leonor; Pimentel, Ana Carolina; Manageiro, Vera; Duarte, Aida; Caniça, Manuela; Vale, Filipa F.Acinetobacter baumannii is a Gram-negative opportunistic pathogen, responsible for nosocomial infections worldwide. In recent years, this microorganism has acquired resistance to various antibiotics, prompting the World Health Organization (WHO) to declare carbapenem-resistant A. baumannii (CRAB) a critical priority microorganism requiring urgent attention and the development of new therapeutic options. Here, we screened for prophages in 158 genomes of A. baumannii, comprising 139 complete genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), and 19 newly sequenced clinical isolates. Additionally, we conducted phylogenetic analyses of prophages, highlighting their diversity and local clustering. The analyzed genomes harbored at least two prophage regions, resulting in the identification of a total of 950 prophage regions, of which 348 were considered complete prophages through software analysis and manual curation, while the remainder may represent prophage remnants. The complete prophages ranged from 28.6 to 103.9 kbp, with an average GC content of 39%. Based on genomic similarity, only 18 complete prophages were taxonomically classified to the genus Vieuvirus. Among all identified complete prophages, we identified 166 genes encoding for putative lysins, while prophage regions that were not considered complete could also harbor putative lysins. These findings highlight the abundance of prophage-encoded lysins in A. baumannii genomes, which are promising therapeutic agents for combating A. baumannii infections, particularly in the face of rising antibiotic resistance.
