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Updated: Jan 27, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Two virulent bacteriophages targeting carbapenem-resistant Raoultella planticola
Cuong V Hoang1, Jonathan Fan1, Lauren Bhasin1
1Department of Microbiology & Plant Pathology, University of California, Riverside, Riverside, CA, United States.
Abstract:
Carbapenem-resistant Raoultella planticola (CRRP) is an emerging nosocomial pathogen with limited therapeutic options. Here, we describe the comparative characterization of two novel virulent bacteriophages, Macy and Sally, both isolated from the same soil microenvironment. Macy exhibits exceptional lytic potency, with a burst size of 8,375 PFU per infected cell, narrow host specificity, and pronounced biofilm-disrupting activity likely mediated by a putative depolymerase. In contrast, Sally displays a broader host range, infecting both R. planticola and R. ornithinolytica (including a clinical CRRP isolate), while maintaining moderate lytic activity, notable acid tolerance, and substantial biofilm reduction. SNP analysis revealed that resistant isolates carried mutations in genes linked to surface polysaccharide biosynthesis and LysR-family transcriptional regulation, conferring resistance at a measurable cost to bacterial growth fitness. Genomic and phylogenomic analyses further revealed distinct evolutionary trajectories: Macy is a large (147.8 kb) member of Straboviridae Straboviridae with a mosaic genome related to Raoultella phages, whereas Sally is a compact (48.5 kb) Casjensviridae phage that is siphovirus more closely aligned with Klebsiella and Enterobacter phages. Pangenomic comparisons highlighted Macy's strain-specific gene expansions versus Sally's cross-genus homology, emphasizing divergent adaptation strategies. Together, these findings illustrate the complementary therapeutic potential of Macy and Sally and establish a genomic and phenotypic foundation for developing effective phage cocktails against multidrug-resistant Raoultella infections.
Insights
Two novel bacteriophages, Macy and Sally, show promise for combating carbapenem-resistant Raoultella planticola (CRRP) infections. Their distinct characteristics offer a foundation for developing phage cocktails against these challenging multidrug-resistant pathogens.
Area of Science:
- Microbiology
- Virology
- Genomics
Background:
- Carbapenem-resistant Raoultella planticola (CRRP) is an emerging nosocomial pathogen posing significant treatment challenges due to limited therapeutic options.
- Bacteriophage therapy presents a potential alternative for combating multidrug-resistant bacterial infections.
Purpose of the Study:
- To comparatively characterize two novel virulent bacteriophages, Macy and Sally, isolated from soil.
- To evaluate their lytic activity, host range, biofilm disruption capabilities, and genomic features.
- To understand the genomic basis of CRRP resistance.
Main Methods:
- Isolation and characterization of bacteriophages Macy and Sally.
- Assessment of lytic potency, burst size, host specificity, and biofilm disruption.
- SNP analysis to identify resistance mechanisms in Raoultella isolates.
- Genomic sequencing, phylogenomic analysis, and pangenomic comparisons.
Main Results:
- Macy demonstrated high lytic potency and biofilm disruption, with narrow host specificity.
- Sally exhibited broader host range, acid tolerance, and significant biofilm reduction.
- CRRP resistance was linked to mutations in polysaccharide biosynthesis and LysR-family regulation genes, impacting bacterial fitness.
- Genomic analysis revealed distinct evolutionary paths for Macy (Straboviridae) and Sally (Casjensviridae).
Conclusions:
- Macy and Sally possess complementary therapeutic potential against multidrug-resistant Raoultella.
- Their distinct genomic and phenotypic profiles provide a foundation for developing effective phage cocktails.
- Understanding resistance mechanisms is crucial for optimizing phage therapy strategies.
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