Therapeutic Potential of a Novel Stenotrophomonas maltophilia Phage XAN_XB1: Isolation, Characterization, Genome Analysis and Evaluation in Mice Model

TL;DR

A new bacteriophage, XAN_XB1, was isolated and shown to effectively combat multidrug-resistant Stenotrophomonas maltophilia infections in mice.

Contribution

XAN_XB1 is a novel lytic phage with broad host range and therapeutic efficacy against drug-resistant S. maltophilia.

Findings

XAN_XB1 exhibits lytic activity across a wide range of temperatures and pH levels.

The phage significantly reduces pulmonary inflammation and bacterial colonization in infected mice.

Genome analysis confirms XAN_XB1 as a new phage species without virulence or resistance genes.

Abstract

A novel lytic bacteriophage, XAN_XB1, was isolated from hospital wastewater through host bacterial enrichment and evaluated for its potential in controlling multidrug-resistant Stenotrophomonas maltophilia infections. Transmission electron microscopy revealed that XAN_XB1 has a long tail, possessing an icosahedral head of ~80 nm in diameter and a tail measuring ~150 nm in length. It produced clear plaques of 0.5–1 mm on host bacterial lawns. Host range analysis demonstrated its ability to infect multiple multidrug-resistant S. maltophilia isolates. Biological characterization showed that the phage is chloroform-insensitive, retains strong lytic activity across a wide temperature (4–60 °C) and pH (3.0–10.0) range, and achieves more rapid host suppression under higher multiplicity of infection (MOI). Whole-genome sequencing determined a ~47 kb double-stranded DNA genome encoding 71 predicted open reading frames, with no known virulence or antibiotic resistance genes. Phylogenetic analysis of MCP and terminase large subunit sequences placed XAN_XB1 in a unique Caudoviricetes, with ANI values below the 95% ICTV threshold verifying its status as a novel phage species. The XAN_XB1 therapy significantly alleviates S. maltophilia infection-induced severe pulmonary inflammatory lesions, high mortality, elevated serum inflammatory factors and massive pulmonary bacterial colonization in male BALB/c mice, confirming its favorable therapeutic effect on such infections. Collectively, these results reveal that is an efficacious candidate for therapeutic development against S. maltophilia infections.

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