Biology subjects

Haines, M. E.

Publications and source records attributed to Haines, M. E..

3 recordsLinked to original sources

bioRxiv2026

Large scale antibiotic-phage synergy studies reveal key combinations for urinary tract infection and urosepsis treatments

The growing problem of AMR infections in healthcare has prompted the search for alternative treatments, with increasing interest in bacteriophages. However, most bacteriophage-antibiotic interactions are incompletely understood, and the benefits of combining them remains context dependent. In this study, we screened thousands of phage-antibiotic combinations to assess interaction outcomes in clinical E. coli and K. pneumoniae isolates. By integrating bacteriophages into an existing, scalable clinical MIC determination platform, we identified shifts in antibiotic MIC and susceptibility, revealing patterns of additivity and antagonism. Overall, interactions showed a species-specific profile; additive interactions predominated, particularly for E. coli. Hierarchical clustering highlighted frequent positive interactions between {beta}-lactams and Tequatroviruses. Notably, closely related phages sometimes displayed divergent phenotypes, indicating that interaction outcomes cannot be inferred solely from taxonomic relatedness or genomic similarity. Taken together, these results establish a foundation for rational, evidence-based development of phage-antibiotic therapies to restore and broaden treatment options against multidrug-resistant infections.

microbiology↗

bioRxiv2025

Bacteriophage pharmacodynamics studied in an in vitro pharmacokinetic model of infection

SynopsisO_ST_ABSBackgroundC_ST_ABSBacteriophage therapy offers an alternative way to counter the menace of increasing antimicrobial resistance. Despite its use in clinical practice for many decades the basic tools to study the translational pharmacodynamics of phages are not available and it is recognised that lack of understanding of phage pharmacokinetic/dynamics (PK/PD) is a severe limitation in individual patient use and clinical trial design. MethodsTraditional in vitro PK/PD evaluation tools were used to assess the antibacterial effect of single exposures of a bacteriophage cocktail against 4 strains of E. coli with potentially different patterns of response to phage. Initially, time-kill curves (TKC) were performed over 48hr and subsequently a dilutional in vitro model (IVM) was used to assess the antibacterial effects over 72hr. ResultsIn TKC, the four E. coli strains showed different patterns of kill and regrowth when exposed to phage with two strains showing a sustained drop in bacterial viable count and two showing initial kill and regrowth. Using the IVM similar bacterial pharmacodynamic patterns were observed, and phage titre increased inversely but consistently with E. coli kill. ConclusionsAn In vitro dilutional model can be used to study the antibacterial effect of a phage cocktail on E.coli showing strain-to-strain variation in bacterial killing and bacteriophage titre. Such models can be used to provide more nuanced information on phage pharmacokinetics/dynamics and translationally useful information for dosing in humans.

microbiology↗

bioRxiv2020

Analysis of selection methods to develop novel phage therapy cocktails against antimicrobial resistant clinical isolates of bacteria

Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as critical for research. Bacteriophages (phages) as viruses that can infect and kill bacteria, could provide an effective tool to tackle these AMR strains. There is currently no gold standard for developing a phage cocktail. Here we describe a novel approach to develop an effective phage cocktail against a set of ESBL-producing E. coli and Klebsiella largely isolated from patients in UK hospitals. By comparing different measures of phage efficacy, we show which are the most robust, and suggest an efficient screening cascade that could be used to develop phage cocktails to target other AMR bacterial species. A target panel of 38 ESBL-producing clinical strains isolated from urine samples was collated and used to test phage efficacy. After an initial screening of 68 phages, six were identified and tested against these 38 strains to determine their clinical coverage and killing efficiency. To achieve this, we assessed four different methods to assess phage virulence across these bacterial isolates. These were the Direct Spot Test (DST), the Efficiency of Plating (EOP) assay, the planktonic killing assay and the biofilm assay. The final ESBL cocktail of six phages could effectively kill 23/38 strains (61%) for Klebsiella 13/19 (68%) and for E. coli 10/19 (53%) based on the planktonic killing assay data. The ESBL E. coli collection had six isolates from the prevalent UTI-associated ST131 sequence type, five of which were targeted effectively by the final cocktail. Of the four methods used to assess phage virulence, the data suggests that planktonic killing assays are as effective as the much more time-consuming EOPs and data for the two assays correlates well. This suggests that planktonic killing is a good proxy to determine which phages should be used in a cocktail. This assay when combined with the virulence index also allows phage synergy to inform cocktail design.

microbiology↗