Biomedical subjects

Vaughn S Cooper

Publications and source records attributed to Vaughn S Cooper.

4 recordsLinked to original sources

PubMed2026

Methods for cost-efficient, whole genome sequencing surveillance for enhanced detection of outbreaks in a hospital setting.

INTRODUCTION: Outbreaks of healthcare-associated infections (HAI) result in substantial patient morbidity and mortality; mitigation efforts by infection prevention teams have the potential to curb outbreaks and prevent transmission to additional patients. The incorporation of whole genome sequencing (WGS) surveillance of suspected high-risk pathogens often identifies outbreaks that are not detected by traditional infection prevention methods and provides evidence for transmission. Our approach to real-time WGS surveillance, the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), has 1) identified serious outbreaks that were otherwise undetected and 2) shown the potential to be cost saving. METHODS: We describe our cost-efficient methods to perform WGS surveillance and data analysis of pathogens for institutions that are interested in expanding infection prevention surveillance. We provide an overview of the weekly workflow of EDS-HAT during two distinct phases over three years. RESULTS: In an average week at our tertiary healthcare system, we sequenced 60 samples at a cost of less than $100 each during Phase 1, and 80 samples for less than $70 each in Phase 2, inclusive of laboratory reagents and staff salaries. The average turnaround time, from sample collection to reporting data to infection prevention, was nine days. CONCLUSIONS: Performing EDS-HAT in real-time can be both feasible and time-efficient. Providing such timely information to aid in outbreak detection could identify transmission events sooner and thus could increase patient safety.

Disease Outbreaks↗

PubMed2026

Chronic suppression of a multidrug-resistant Pseudomonas aeruginosa in prosthetic joint infection using personalized bacteriophage treatment.

Multidrug resistant (MDR) bacterial infections without antibiotic options are a public health emergency. Infections associated with medical implants serve as an example. Conventional antibiotics have limited ability to eradicate these infections as they are associated with antibiotic-tolerant biofilms. Here, we report the use of bacteriophage therapy for the treatment of a MDR, non-operable Pseudomonas aeruginosa periprosthetic joint infection that had failed multiple antibiotic and surgical interventions. Treatment with intermittent bacteriophage therapy alone without antibiotics over a 2 year time period resulted in clinical resolution of the infection, but not microbiological eradication. Bacteriophage therapy established this control, in part, by altering virulence as defined by disease severity and symptoms and disrupting biofilm. Whole genome sequencing demonstrated the continued presence of bacteriophage during treatment. This provides preliminary evidence that bacteriophage therapy can be used to treat MDR infections in salvage cases when surgical and antibiotic options do not exist.

Humans↗

PubMed2025

Pseudomonas aeruginosa biofilm-deficient mutants undergo parallel adaptation during chronic infection.

Pseudomonas aeruginosa readily adapts to infection by acquiring stable and heritable mutations. Previously, we discovered that the first adaptations in a porcine wound model were rugose small-colony variants (RSCVs) caused by mutations in the wsp operon. These mutants overproduce Pel and Psl biofilm exopolysaccharides that improve defense against host responses. To identify other mechanisms of host adaptation that lead to hyperbiofilm phenotypes, we created a mutant with an activated wsp pathway but unable to produce these exopolysaccharides (ΔwspFΔpelAΔpslBCD). Porcine wounds were infected with this mutant and biopsies were sampled at days 7, 14 and 35. Small colony variants were isolated from the wound, and whole genome sequencing revealed these variants had acquired mutations in genes in lipopolysaccharide and type IV pili biosynthesis, with wzy and pilU genes being most commonly targeted. pilU mutants were associated with a hyperbiofilm phenotype that outcompeted the parental strain, and wzy mutants were associated with a hyperbiofilm phenotype and increased tolerance to host antimicrobial products. We further identified that several variants had acquired large genome deletions that spanned up to 320 consecutive genes and other variants with high copy numbers of Pf6 filamentous phage. Together our results suggest that the hyperbiofilm phenotype is adaptive in chronic infections and that P. aeruginosa has redundant and diverse pathways to generate this phenotype.

adaptation↗

PubMed2025

Filamentous cheater phages drive bacterial and phage populations to lower fitness.

Many bacteria carry phage genome(s) in their chromosome, which intertwines the fitness of the bacterium and the phage. Most Pseudomonas aeruginosa strains carry filamentous phages called Pf that establish chronic infections and do not require host lysis to spread. However, spontaneous mutations in the Pf repressor gene (pf5r) can allow extreme phage production that slows bacterial growth and increases cell death, violating an apparent détente between bacterium and phage. We observed this paradoxical outcome in an evolution experiment with P. aeruginosa in media simulating nutrients from the cystic fibrosis airway. Bacteria containing pf5r mutant phage grow to a lower density but directly outcompete their ancestor and convert them into pf5r mutants via phage superinfection. Reduced fitness therefore spreads throughout the bacterial population, driven by weaponized Pf. Yet high intracellular phage replication facilitates another evolutionary conflict: "cheater miniphages" lacking capsid genes and the superinfection exclusion gene (pfsE) invade populations of full-length phages within cells. Although bacteria containing both full-length phages and miniphages are most immune to superinfection by limiting the Pf receptor, this hybrid vigor is extremely unstable, as a classic Tragedy of the Commons scenario ensues that causes complete prophage loss. The entire cycle - from phage hyperactivation to miniphage invasion to prophage loss - can occur within 24h, showcasing rapid coevolution between bacteria and their filamentous phages. This study demonstrates that P. aeruginosa, and potentially many other bacterial species that carry filamentous prophages, risk being exploited by these phages in a runaway process that reduces fitness of both host and virus.

Inoviridae↗