Srinivasa, V. R. | Search bioRxiv

bioRxiv2024

Harnessing the diversity of Burkholderia spp. prophages for therapeutic potential

Burkholderia spp. are often resistant to antibiotics, and infections with these organisms are difficult to treat. A potential alternative treatment for Burkholderia spp. infections is bacteriophage (phage) therapy; however, it can be difficult to locate phages that target these bacteria. Prophages incorporated into the bacterial genome have been identified within Burkholderia spp. and may represent a source of useful phages for therapy. Here we investigate whether prophages within Burkholderia spp. clinical isolates can kill conspecific and heterospecific isolates. Thirty-two Burkholderia spp. isolates were induced for prophage release, and harvested prophages were tested for lytic activity against the same 32 isolates. Lytic phages were passaged and their host ranges were determined, resulting in four unique phages of prophage origin that showed different ranges of lytic activity. We also analyzed the prophage content of 35 Burkholderia spp. clinical isolate genomes, and identified several prophages present in the genomes of multiple isolates of the same species. Finally, we observed that B. cenocepacia isolates were more phage-susceptible than Burkholderia multivorans isolates. Overall, our findings suggest that prophages present within Burkholderia spp. genomes are a potentially useful starting point for the isolation and development of novel phages for use in phage therapy.

microbiology↗

bioRxiv2021

Genomic diversity of hospital-acquired infections revealed through prospective whole genome sequencing-based surveillance

Healthcare-associated infections (HAIs) cause mortality, morbidity, and waste of healthcare resources. HAIs are also an important driver of antimicrobial resistance, which is increasing around the world. Beginning in November 2016, we instituted an initiative to detect outbreaks of HAI using prospective whole genome sequencing-based surveillance of bacterial pathogens collected from hospitalized patients. Here we describe the biodiversity of bacteria sampled from hospitalized patients at a single center, as revealed through systematic analysis of their genomes. We sequenced the genomes of 3,004 bacterial isolates from hospitalized patients collected over a 25-month period. We identified bacteria belonging to 97 distinct species, which were distributed among 14 species groups. Within these groups, isolates could be distinguished from one another by both average nucleotide identity (ANI) and principal component analysis of accessory genes (PCA-A). Genetic distances between isolates and rates of evolution varied between different species, which has implications for the selection of distance cut-offs for outbreak analysis. Antimicrobial resistance genes and the sharing of mobile genetic elements between different species were frequently observed. Overall, this study describes the population structure of pathogens circulating in a single healthcare setting, and shows how investigating microbial population dynamics can inform genomic epidemiology studies. ImportanceHospitalized patients are at increased risk of becoming infected with antibiotic-resistant organisms. We used whole-genome sequencing to survey and compare over 3,000 bacterial isolates collected from hospitalized patients at a large medical center over a two-year period. We identified nearly 100 different bacterial species, suggesting that patients can be infected with a wide variety of different organisms. When we examined how genetic relatedness differed between species, we found that different species are likely evolving at different rates within our hospital. This is significant because the identification of bacterial outbreaks in the hospital currently relies on genetic similarity cut-offs, which are often applied uniformly across organisms. Finally, we found that antibiotic resistance genes and mobile genetic elements were abundant among the bacterial isolates we sampled. Overall, this study provides an in-depth view of the genomic diversity and evolution of bacteria sampled from hospitalized patients, as well as genetic similarity estimates that can inform hospital outbreak detection and prevention efforts.

microbiology↗