Unlabelled: Bacteriophages (phages) are bacterial-specific viruses that can be used alone or with antibiotics to reduce bacterial load. Most phages are unsuitable for therapy because they are "temperate" and can integrate into the host genome, forming a lysogen that is protected from subsequent phage infections. However, integrated phages can be awakened by stressors such as antibiotics. Supported by this interaction, here we explore the potential use of combined temperate phage and antibiotic against the multi-drug-resistant pathogen, . In all, thirty-nine temperate phages were isolated from clinical strains, and a subset was screened for synergy with six antibiotics (ciprofloxacin, levofloxacin, meropenem, piperacillin, tobramycin, and polymyxin B), using checkerboard assays. Interestingly, our screen identified phages that can synergize with each antibiotic, despite their widely differing targets; however, these are highly phage-antibiotic and phage-host pairing specific. Screening across multiple clinical strains reveals that temperate phages can reduce the antibiotic minimum inhibitory concentration up to 32-fold, even in a resistant isolate, functionally re-sensitizing the bacterium to the antibiotic. Meropenem and tobramycin did not reduce the frequency of lysogens, suggesting a mechanism of action independent of the temperate nature of the phages. By contrast, ciprofloxacin and piperacillin were able to reduce the frequency of lysogeny, the former by inducing phages-as previously reported in . Curiously, synergy with piperacillin reduced lysogen survivors, but not by inducing the phages, suggesting an alternative mechanism for biasing the phage lysis-lysogeny equilibrium. Overall, our findings indicate that temperate phages can act as adjuvants in clinically relevant pathogens, even in the presence of antibiotic resistance, thereby drastically expanding their therapeutic potential.
Importance: The recent discovery that otherwise therapeutically unusable temperate phages can potentiate the activity of antibiotics, resulting in a potent synergy, has only been tested in , and with a single model phage. Here, working with clinical isolates of and phages from these isolates, we highlight the broad applicability of this synergy-across a variety of mechanisms but also highlight the limitations of predicting the phage, host, and antibiotic combinations that will synergize.
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http://dx.doi.org/10.1128/mbio.02559-24 | DOI Listing |
mBio
December 2024
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Unlabelled: Bacteriophages (phages) are bacterial-specific viruses that can be used alone or with antibiotics to reduce bacterial load. Most phages are unsuitable for therapy because they are "temperate" and can integrate into the host genome, forming a lysogen that is protected from subsequent phage infections. However, integrated phages can be awakened by stressors such as antibiotics.
View Article and Find Full Text PDFMicrobiol Resour Announc
December 2024
Department of Microbiology and Hygiene, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh.
A lytic bacteriophage, BAU.Micro_SLP-22, was isolated from drain water in search of bio-controlling agents against avian salmonellosis. The phage genome is comprised of 59,738 bp with 56.
View Article and Find Full Text PDFMicrobiol Resour Announc
December 2024
Microbial Genetic Division, Institute of Genetic Resources, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
GBlys is a lysogenic strain of the temperate phage phiOH2, which is 3,644,428 bp long, has a GC content of 52%, and contains 3,595 predicted protein-coding genes. Here, we report a resequenced GBlys genome obtained by deep sequencing with long and short reads.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Microbiology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology-State Research Institute, Rakowiecka 36 Str., 02-532 Warsaw, Poland.
is one of the main foodborne pathogens. Irrational antibiotic management has led to an increase in the incidence of multidrug-resistant strains. Bacteriophages may be an alternative method of food biopreservation and contribute to reducing the number of food poisonings requiring pharmacotherapy.
View Article and Find Full Text PDFGut Microbes
December 2024
State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, P. R China.
Prophages, which are an existing form of temperate phages that integrate into host genomes, have been found extensively present in diverse bacterial species. The human gut microbiome, characterized by its complexity, dynamism, and interconnectivity among multiple species, remains inadequately understood in terms of the global landscape of bacterial prophages. Here, we analyzed 43,942 human gut-derived bacterial genomes (439 species of 12 phyla) and identified 105,613 prophage regions in ~ 92% of them.
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