Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae DOI Creative Commons

Aye Mya Sithu Shein,

Dhammika Leshan Wannigama, Cameron Hurst

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 22, 2024

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing activities against 81.3% (n = 26) 78.1% 25) 32 XDR K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 K2/wzi-2. Both short replication times, large burst sizes rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both genetically distinct Myoviridae Podoviridae family, the lack toxin, virulence, lysogeny antibiotic resistance genes. These characteristics highlighted their potential utilizing phage therapy pneumoniae. Although cocktail combining vB_kpnM_05 provided bacteriolysis longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development phages' selection pressures. Future study will be undertaken elucidate precise mechanisms developed associated fitness cost. Remarkably, amikacin at sub-inhibitory concentrations produced potent synergy completely suppressing vitro. Our demonstrated prophylactic effectiveness cocktail-amikacin combination as alternative strategy overcoming bacteremia carbapenemase colistin vivo.

Language: Английский

Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation DOI Creative Commons
Amanda Carroll‐Portillo, October Barnes, Cristina Coffman

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 134 - 134

Published: Jan. 19, 2025

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the system through pathogen associated (PAMP) receptors (i.e., TLRs). Given reside in same body niches as bacteria, they share propensity stimulate quench responses depending on nature their interactions host cells. While vitro research focuses outcomes direct application interest, potential impact transcytosis intestinal barrier has yet be considered. As a necessary step healthy systems for access by phage underlying cell populations, it imperative understand how this may play role activation. We compared activation macrophages (as measured TNFα secretion) following those stimulated incubation transcytosed polarized Caco2 epithelial model. Our results demonstrate capable activating secretion upon contact maintain stimulatory capability transcytosis. Furthermore, enhanced occurring an equivalent multiplicity directly applied phage.

Language: Английский

Citations

0

Comprehensive Review on Phage Therapy and Phage-Based Drug Development DOI Open Access
Longzhu Cui, Shinya Watanabe, Kazuhiko Miyanaga

et al.

Published: Aug. 27, 2024

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against rising threat multidrug-resistant (MDR) bacteria. This comprehensive review explores historical context, modern resurgence phage and phage-facilitated advancements in medical technological fields. It details mechanisms action applications phages treating MDR particularly those associated with biofilms intracellular pathogens. The further highlights innovative uses vaccine development, cancer gene delivery vectors. Despite its targeted efficient approach, therapy faces challenges related stability, immune response, regulatory approval. By examining these areas detail, this underscores immense potential remaining hurdles integrating phage-based therapies into practices.

Language: Английский

Citations

3

Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae DOI Creative Commons

Aye Mya Sithu Shein,

Dhammika Leshan Wannigama, Cameron Hurst

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 22, 2024

The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing activities against 81.3% (n = 26) 78.1% 25) 32 XDR K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 K2/wzi-2. Both short replication times, large burst sizes rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both genetically distinct Myoviridae Podoviridae family, the lack toxin, virulence, lysogeny antibiotic resistance genes. These characteristics highlighted their potential utilizing phage therapy pneumoniae. Although cocktail combining vB_kpnM_05 provided bacteriolysis longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development phages' selection pressures. Future study will be undertaken elucidate precise mechanisms developed associated fitness cost. Remarkably, amikacin at sub-inhibitory concentrations produced potent synergy completely suppressing vitro. Our demonstrated prophylactic effectiveness cocktail-amikacin combination as alternative strategy overcoming bacteremia carbapenemase colistin vivo.

Language: Английский

Citations

3