Molecular Studies of Phages-Klebsiella pneumoniaein a Mucoid Environment: Innovative use of mucolytic agents prior to the administration of lytic phages

• DOI: 10.1101/2023.08.02.551690
• Publication Date: 2023-08-04T12:20:11Z
• Authors: Olga Pacios; Lucía Blasco; Concha Ortiz-Cart...; Inés Bleriot; Laura Fernández-G...; María López; Antonio Barrio-Pu...; Álvaro Pascual; Felipe Fernández ...; Luis Martínez-Mar...; Belén Aracil; Jesús Oteo-Iglesias; María Tomás
• Keywords: Lytic cycle; Phage therapy; Lysogenic cycle

Abstract Mucins are important glycoproteins that form a protective layer throughout the gastrointestinal and respiratory tracts. There is scientific evidence of increase in phage-resistance presence mucin for some bacterial pathogens. Manipulation composition may ultimately influence effectiveness phage therapy. In this work, two clinical strains K. pneumoniae (K3574 K3325), were exposed to lytic bacteriophage vB_KpnS-VAC35 absence on long-term co-evolution assay, an attempt mimic vitro exposure mucins bacteria their phages face vivo . Enumerations counts at regular time intervals conducted, extraction genomic DNA co- evolved phage, both was performed. We determined frequency phage-resistant mutants including mucolytic agent (N-acetyl L-cysteine, NAC), sequenced these conditions using Nanopore. phenotypically demonstrated induces emergence resistance against phages, effectively decreased NAC. addition, analysis revealed genes relevant development evolution, with special focus mucoid environment. Genes involved metabolism carbohydrates mutated mucin. conclusion, use agents prior administration could be interesting therapeutic option when addressing infections environments where overproduced.