2026-05-16T22:13:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/169572024-11-28T16:50:08Zcom_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 Pacios, Olga author Blasco, Lucía author Ortiz Cartagena, Concha author Bleriot, Inés author Fernández-García, Laura author López, María author Barrio-Pujante, Antonio author Fernández-Cuenca, Felipe author Aracil, Belen author Oteo-Iglesias, Jesus author Tomás, María author 2023 Mucins are important glycoproteins that form a protective layer throughout the gastrointestinal and respiratory tracts. There is scientific evidence of increase in phage-resistance in the presence of mucin for some bacterial pathogens. Manipulation in mucin composition may ultimately influence the effectiveness of phage therapy. In this work, two clinical strains of K. pneumoniae (K3574 and K3325), were exposed to the lytic bacteriophage vB_KpnS-VAC35 in the presence and absence of mucin on a long-term co-evolution assay, in an attempt to mimic in vitro the exposure to mucins that bacteria and their phages face in vivo. Enumerations of the bacterial and phage counts at regular time intervals were conducted, and extraction of the genomic DNA of co-evolved bacteria to the phage, the mucin and both was performed. We determined the frequency of phage-resistant mutants in the presence and absence of mucin and including a mucolytic agent (N-acetyl L-cysteine, NAC), and sequenced them using Nanopore. We phenotypically demonstrated that the presence of mucin induces the emergence of bacterial resistance against lytic phages, effectively decreased in the presence of NAC. In addition, the genomic analysis revealed some of the genes relevant to the development of phage resistance in long-term co-evolution, with a special focus on the mucoid environment. Genes involved in the metabolism of carbohydrates were mutated in the presence of mucin. In conclusion, the use of mucolytic agents prior to the administration of lytic phages could be an interesting therapeutic option when addressing K. pneumoniae infections in environments where mucin is overproduced. Front Microbiol. 2023 Oct 11:14:1286046. 10.3389/fmicb.2023.1286046 1664-302X Frontiers in microbiology 37886069 http://hdl.handle.net/20.500.12105/16957 Klebsiella pneumoniae Lytic bacteriophages Phage resistance Co-evolution Mucin n-acetyl cysteine Molecular studies of phages-Klebsiella pneumoniae in mucoid environment: innovative use of mucolytic agents prior to the administration of lytic phages