Phage therapy for multidrug-resistant Serratia marcescens infection: mechanisms, preclinical evidence, and translational challenges
- 1School of Ethnic Medicine, Yunnan Minzu University
- 2Faculty of Life Science and Technology, Kunming University of Science and Technology
Abstract
Multidrug-resistant and carbapenem-resistant Serratia marcescens ( S. marcescens ) infections are increasingly difficult to treat because of intrinsic and acquired antimicrobial-resistance mechanisms, limited therapeutic options, and the organism’s capacity to persist within biofilms. Phage therapy has therefore emerged as a potential precision antimicrobial strategy against refractory S. marcescens infections. This narrative review critically examines the molecular basis, preclinical development, and translational potential of phage therapy targeting multidrug-resistant S. marcescens . Particular emphasis is placed on phage adsorption and receptor recognition, bacterial anti-phage defense systems, capsule- and biofilm-associated resistance, phage-encoded depolymerases, host-range limitations, phage screening and cocktail design, phage–antibiotic interactions, and available preclinical and clinical evidence. Current findings support the biological plausibility of this approach, particularly when strictly lytic phages are matched to the infecting clinical isolate and delivered locally in combination with antibiotics. However, the clinical evidence remains limited primarily to individual compassionate-use reports, and the therapeutic contribution of phages cannot be clearly distinguished from that of concomitant antibiotics, drainage procedures, or supportive care. Additional barriers include the emergence of phage resistance, variable pharmacokinetics, immune-mediated phage clearance, limited standardized susceptibility testing, and manufacturing and regulatory challenges. Future research should prioritize receptor-informed phage selection, representative clinical isolate panels, rationally designed phage cocktails, standardized pharmacokinetic and pharmacodynamic evaluation, and prospective controlled clinical studies. Precision phage therapy, engineered phages, curated phage libraries, and harmonized regulatory pathways may ultimately facilitate the transition of phage therapy from an individualized salvage intervention to a reproducible treatment strategy for multidrug-resistant S. marcescens infections.
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BibTeX
@article{zhang2026phage,
title = {{Phage therapy for multidrug-resistant Serratia marcescens infection: mechanisms, preclinical evidence, and translational challenges}},
author = {Shengting Zhang and Huili Tao and Sha Zhao and Yunlin Wei},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1959850},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1959850/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phage therapy for multidrug-resistant Serratia marcescens infection: mechanisms, preclinical evidence, and translational challenges
AU - Shengting Zhang
AU - Huili Tao
AU - Sha Zhao
AU - Yunlin Wei
PY - 2026
DA - 2026/10/20
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1959850
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1959850/full
AB - Multidrug-resistant and carbapenem-resistant Serratia marcescens ( S. marcescens ) infections are increasingly difficult to treat because of intrinsic and acquired antimicrobial-resistance mechanisms, limited therapeutic options, and the organism’s capacity to persist within biofilms. Phage therapy has therefore emerged as a potential precision antimicrobial strategy against refractory S. marcescens infections. This narrative review critically examines the molecular basis, preclinical development, and translational potential of phage therapy targeting multidrug-resistant S. marcescens . Particular emphasis is placed on phage adsorption and receptor recognition, bacterial anti-phage defense systems, capsule- and biofilm-associated resistance, phage-encoded depolymerases, host-range limitations, phage screening and cocktail design, phage–antibiotic interactions, and available preclinical and clinical evidence. Current findings support the biological plausibility of this approach, particularly when strictly lytic phages are matched to the infecting clinical isolate and delivered locally in combination with antibiotics. However, the clinical evidence remains limited primarily to individual compassionate-use reports, and the therapeutic contribution of phages cannot be clearly distinguished from that of concomitant antibiotics, drainage procedures, or supportive care. Additional barriers include the emergence of phage resistance, variable pharmacokinetics, immune-mediated phage clearance, limited standardized susceptibility testing, and manufacturing and regulatory challenges. Future research should prioritize receptor-informed phage selection, representative clinical isolate panels, rationally designed phage cocktails, standardized pharmacokinetic and pharmacodynamic evaluation, and prospective controlled clinical studies. Precision phage therapy, engineered phages, curated phage libraries, and harmonized regulatory pathways may ultimately facilitate the transition of phage therapy from an individualized salvage intervention to a reproducible treatment strategy for multidrug-resistant S. marcescens infections.
SN - 1664-302X
ER -