Publication Database

Identification of the genetic basis of phage resistance in sequentially generated phage-resistant Klebsiella pneumoniae using an established phage library (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Zhao, Wenbo

Du, Congyang

Chen, Zheng

Zhao, Yunze

Schwarz, Stefan (WE 7)

Yao, Hong

Li, Chenglong

Xu, Chunyan

Du, Xiang-Dang

Quelle

Antibiotics : open access journal

Bandzählung: 14

Heftzählung: 11

Seiten: Artikel 1056 (15 Seiten)

ISSN: 2079-6382

Sprache

Englisch

Verweise

URL (Volltext): https://www.mdpi.com/2079-6382/14/11/1056

DOI: 10.3390/antibiotics14111056

Pubmed: 41301552

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Objectives: To explore the genetic basis of phage resistance in sequentially generated capsular mutants of phage-resistant Klebsiella pneumoniae using an established phage library. Methods: Sequential induction strategies were employed to obtain phage-resistant K. pneumoniae capsular mutants by exposing ST11-K64 K. pneumoniae Kp2325 to different single phages. Whole genome sequencing and bioinformatic analysis were used to elucidate the capsular-related genetic changes in phage-resistant mutants. Phenotypic changes were assessed through gene complementation, growth assays, phage cleavage spectrum analysis, TEM for phage morphology, CPS analysis, biofilm formation, and virulence assays. Results: Three sequentially generated phage-resistant K. pneumoniae capsular mutants were obtained, designated R1, R2 and R3. The narrowing of the phage cleavage spectrum and the evolutionary trade-offs of biological phenotypes were observed. Key genetic changes included: (1) ISKpn26 insertion disrupting wcaJ in R1; (2) combined wcaJ insertion and 9-bp deletion in waaH in R2; and (3) CPS gene cluster deletion in R3 were identified as key mechanisms of phage resistance in K. pneumoniae mutants R1, R2 and R3, respectively. Conclusions: Sequential exposure to different single phages led to rapid evolution of phage resistance in K. pneumoniae via genetic mutations that disrupt capsular synthesis. These findings highlight the critical role of bacterial capsule in phage-host interactions and emphasize the need to use phage cocktails targeting different types of receptors to counteract the evolution of bacterial defense mechanisms in phage therapy.