scholarly journals Isolation and characterisation of Klebsiella phages for phage therapy

2020 ◽  
Author(s):  
Eleanor Townsend ◽  
Lucy Kelly ◽  
Lucy Gannon ◽  
George Muscatt ◽  
Rhys Dunstan ◽  
...  

AbstractKlebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection and sepsis. Bacteriophage (phage) therapy is being considered as a primary option for the treatment of drugresistant infections of these types. We report the successful isolation and characterisation of 30 novel, genetically diverse Klebsiella phages. The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected up to 11 of the 18 Klebsiella capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Of the Klebsiella-infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Importantly, when applied alone, none of the characterised phages were able to suppress the growth of Klebsiella for more than 12 hours, with some phages only able to suppress growth for 3 hours, likely due to inherent ease of Klebsiella to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat Klebsiella infections.

2021 ◽  
Author(s):  
Michael L. Neugent ◽  
Ashwani Kumar ◽  
Neha V. Hulyalkar ◽  
Kevin C. Lutz ◽  
Vivian H. Nguyen ◽  
...  

Community-acquired urinary tract infection (UTI) is among the most common bacterial infections observed in humans. Postmenopausal women are a rapidly growing and underserved demographic group who are severely affected by rUTI with a >50% recurrence rate. In this population, rUTI can persist for years, reducing quality of life and imposing a significant healthcare burden. rUTI is most often treated by long-term antibiotic therapy, but development of antibiotic resistance and allergy leave physicians with fewer treatment options. The female urobiome has been identified as a key component of the urogenital environment. However, structural and functional changes in the urobiome underlying rUTI susceptibility in postmenopausal women are not well understood. Here, we used strictly curated, controlled cross-sectional human cohorts of postmenopausal women, urobiome whole genome (shotgun) metagenomic sequencing (WGMS), advanced urine culturing techniques, extensive biobanking of >900 patient-derived urinary bacterial and fungal isolates, and mass spectrometry-based estrogen profiling to survey the urobiome in rUTI patients during infection relapse and remission as well as healthy comparators with no lifetime history of UTI. Our results suggest that a history of rUTI strongly shapes the taxonomic and functional ecology of the urobiome. We also find a putative protective commensal population, consisting of species known to convey protection against bacterial vaginosis such as Lactobacillus crispatus, within the urobiome of women who do not experience UTI. Integration of clinical metadata detected an almost exclusive enrichment of putative protective species belonging to the genus, Lactobacillus, in women taking estrogen hormone therapy (EHT). We further show that the urobiome taxonomic ecology is shaped by EHT, with strong enrichments of putatively protective lactobacilli, such as L. crispatus and L. vaginalis. Integrating quantitative metabolite profiling of urinary estrogens with WGMS, we observed robust associations between urobiome taxa, such as Bifidobacterium breve and L. crispatus, and urinary estrogen conjugate concentrations, suggesting that EHT strongly alters the taxonomic composition of the female urobiome. We have further used functional metagenomic profiling and patient-derived isolate phenotyping to identify microbial metabolic pathways, antimicrobial resistance genes (ARGs), and clinically relevant antimicrobial resistance phenotypes enriched between disease-states. Our data suggest distinct metabolic and ARG signatures of the urobiome associated with current rUTI status and history. Taken together, our data suggests that rUTI history and estrogen use strongly shape the functional and taxonomic composition of the urobiome in postmenopausal women.


2018 ◽  
Vol 60 (5) ◽  
pp. 418-422 ◽  
Author(s):  
Jun Wang ◽  
Lijiao He ◽  
Jintong Sha ◽  
Haobo Zhu ◽  
Liqu Huang ◽  
...  

2009 ◽  
Vol 5 (2) ◽  
pp. 49-54
Author(s):  
Padma Shrestha ◽  
S. Malla ◽  
S. Basnyat ◽  
S. Dumre ◽  
B. Upadhyay ◽  
...  

Not uploaded.Key words: Urinary tract infection; Multidrug-resistanceDOI: 10.3126/jnhrc.v5i2.2471Journal of Nepal Health Research Council (JNHRC) Vol. 5, No.2, October 2007 49-54


2016 ◽  
Vol 171 ◽  
pp. 116-121 ◽  
Author(s):  
Nader Shaikh ◽  
Alejandro Hoberman ◽  
Ron Keren ◽  
Anastasia Ivanova ◽  
Nathan Gotman ◽  
...  

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Thiago G. S. Paim ◽  
Luiza Pieta ◽  
Janira Prichula ◽  
Gustavo E. Sambrano ◽  
Renata Soares ◽  
...  

We report here a draft genome sequence ofEnterococcus faecalisstrain F165 isolated from a urine specimen in South Brazil. The genome size was 3,049,734 bp, with a G+C content of 37.38%, and genes related to antimicrobial resistance and adherence were found in the strain. These findings are consistent with pathogenesis ofE. faecalisspecies.


Sign in / Sign up

Export Citation Format

Share Document