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PubMed2026

Differential virulence potential of different clades of multidrug-resistant Klebsiella pneumoniae ST258.

Klebsiella pneumoniae (KP) isolates belonging to multi-locus sequence type 258 (ST258) are a frequent cause of hospital-associated outbreaks and display extensive multidrug resistance. The KP ST258 lineage consists of two genetically distinct clades, called Clade 1 and Clade 2. These two clades are genetically related to one another, but are historically distinguished by having different capsular polysaccharide types. While bacteria belonging to both clades are isolated from clinical infections, Clade 2 is isolated more frequently compared to Clade 1. To investigate drivers of this difference in clade prevalence, we collected 172 clinical KP ST258 isolates from patients at a single medical center. Clinical review showed that patients infected with Clade 2 isolates were more acutely ill than Clade 1-infected patients, despite having fewer comorbidities. We also found that Clade 2 isolates were more resistant to killing by human serum, despite binding more complement protein C3 than Clade 1 isolates. Additionally, mice infected with a Clade 2 isolate had increased bacterial dissemination from the lungs to the liver and spleen than mice infected with a Clade 1 isolate, and this dissemination required an intact capsule locus. Increased dissemination in mice was not due to differential serum killing, as mouse serum was unable to kill isolates of either clade, but dissemination was associated with decreased macrophage uptake of the Clade 2 isolate. Taken together, these data suggest that KP ST258 Clade 2 is more virulent than Clade 1, although the specific mechanisms at play appear to differ between mice and humans.IMPORTANCEKP ST258 is an epidemic lineage of multidrug-resistant gram-negative bacteria that has caused numerous outbreaks in hospitals around the world. The KP ST258 population is divided into two genetically related but distinct clades, which differ primarily in their capsule type. In this study, we found that patients infected with one of the KP ST258 clades were more acutely ill than patients infected with the other clade. We also observed clade-specific differences both in killing by human serum and in bacterial dissemination in a mouse model of pneumonia. Finally, we identified important limitations in the use of mouse models to study host defenses against multidrug-resistant KP infection. Overall, this work underscores the importance of capsule composition in KP ST258 virulence, identifies differences in the host response to KP infection between mice and humans, and highlights a potential role for complement-targeting immunotherapeutics in the treatment of KP infections.

Klebsiella pneumoniae↗

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↗

PubMed2026

Differential virulence potential of different clades of multidrug-resistant Klebsiella pneumoniae ST258.

Klebsiella pneumoniae (KP) isolates belonging to multi-locus sequence type 258 (ST258) are a frequent cause of hospital-associated outbreaks and display extensive multidrug resistance. The KP ST258 lineage consists of two genetically distinct clades, called Clade 1 and Clade 2. These two clades are genetically related to one another, but are historically distinguished by having different capsular polysaccharide types. While bacteria belonging to both clades are isolated from clinical infections, Clade 2 is isolated more frequently compared to Clade 1. To investigate drivers of this difference in clade prevalence, we collected 172 clinical KP ST258 isolates from patients at a single medical center. Clinical review showed that patients infected with Clade 2 isolates were more acutely ill than Clade 1-infected patients, despite having fewer comorbidities. We also found that Clade 2 isolates were more resistant to killing by human serum, despite binding more complement protein C3 than Clade 1 isolates. Additionally, mice infected with a Clade 2 isolate had increased bacterial dissemination from the lungs to the liver and spleen than mice infected with a Clade 1 isolate, and this dissemination required an intact capsule locus. Increased dissemination in mice was not due to differential serum killing, as mouse serum was unable to kill isolates of either clade, but dissemination was associated with decreased macrophage uptake of the Clade 2 isolate. Taken together, these data suggest that KP ST258 Clade 2 is more virulent than Clade 1, though the specific mechanisms at play appear to differ between mice and humans.

Klebsiella pneumoniae↗

PubMed2025

Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.

Klebsiella pneumoniae (KP) is a Gram-negative bacterium that commonly resides in the human gastrointestinal tract and can also act as an opportunistic pathogen and cause extra-intestinal infections. KP poses a global health threat because it causes both hospital- and community-acquired infections in immune-competent and immunocompromised hosts. These infections can be multidrug-resistant and/or hypervirulent, making KP infections difficult to treat and deadly. In the absence of effective treatments for recalcitrant KP infections, bacteriophage (phage) therapy is gaining attention as a promising alternative. In this review, we evaluate KP epidemiology and epitope diversity, discuss interactions between KP-targeting phages and their bacterial hosts from an eco-evolutionary perspective, and summarize recent efforts in phage therapy for treating KP infections. We also discuss novel approaches, including genetic engineering and machine learning, as initial steps toward developing KP-targeting phage therapy as a precision medicine approach for an emerging and dangerous pathogen.

Phage Therapy↗