2026-06-14T03:54:32Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/265922025-12-18T12:59:50Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16958col_20.500.12105_16985

00925njm 22002777a 4500 dc Barrio-Pujante, Antonio author Bleriot, Inés author Blasco, Lucía author Fernández-García, Laura author Pacios, Olga author Ortiz-Cartagena, Concha author Cuenca, Felipe Fernández author Oteo-Iglesias, Jesus author Tomás, María author 2024 Background: Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms. Results: Cinnamaldehyde (CAD) was added to K. pneumoniae cultures to inhibit QS and thus demonstrate the role of the signaling system in regulating the anti-phage defense mechanism. The QS inhibitory activity of CAD in K. pneumoniae was confirmed by a reduction in the quantitative expression of the lsrB gene (AI-2 pathway) and by proteomic analysis. The infection assays showed that the phage was able to infect a previously resistant K. pneumoniae strain in the cultures to which CAD was added. The results were confirmed using proteomic analysis. Thus, anti-phage defense-related proteins from different systems, such as cyclic oligonucleotide-based bacterial anti-phage signaling systems (CBASS), restriction-modification (R-M) systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, and bacteriophage control infection (BCI), were present in the cultures with phage but not in the cultures with phage and CAD. When the QS and anti-phage defense systems were inhibited by the combined treatment, proteins related to phage infection and proliferation, such as the tail fiber protein, the cell division protein DamX, and the outer membrane channel protein TolC, were detected. Conclusion: Inhibition of QS reduces phage resistance in K. pneumoniae, resulting in the infection of a previously resistant strain by phage, with a significant increase in phage proliferation and a significant reduction in bacterial growth. QS inhibitors could be considered for therapeutic application by including them in phage cocktails or in phage-antibiotic combinations to enhance synergistic effects and reduce the emergence of antimicrobial resistance. Barrio-Pujante A, Bleriot I, Blasco L, Fernández-Garcia L, Pacios O, Ortiz-Cartagena C, Cuenca FF, Oteo-Iglesias J, Tomás M. Regulation of anti-phage defense mechanisms by using cinnamaldehyde as a quorum sensing inhibitor. Front Microbiol. 2024 Jun 26;15:1416628. 10.3389/fmicb.2024.1416628 1664-302X Frontiers in microbiology 38989015 https://hdl.handle.net/20.500.12105/26592 Klebsiella pneumoniae Anti-phage defense mechanisms Cinnamaldehyde Phage resistance Proteome Quorum sensing Regulation of anti-phage defense mechanisms by using cinnamaldehyde as a quorum sensing inhibitor