Genomic characterization of a new phage BUCT541 against Klebsiella pneumoniae K1-ST23 and efficacy assessment in mouse and Galleria mellonella larvae

Pu, Mingfang; Li, Yahao; Han, Pengjun; Lin, Wei; Geng, Ronghua; Qu, Fen; An, Xiaoping; Song, Lihua; Tong, Yigang; Zhang, Shuyan; Cai, Zhen; Fan, Hao

doi:10.3389/fmicb.2022.950737

Cited by 12 publications

(14 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The higher doses of PhC therapy administered were most effective at increasing the survival of G. mellonella compared with the lower doses of PhC. This association has also been reported in previous studies of phage therapy in G. mellonella [35,39,40]. This is potentially due to increased bacteria-phage interactions that may occur as a result of an increased concentration of phage compared with low-dose phage therapy [13].…”

Section: Discussionsupporting

confidence: 78%

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

Kelly,

Jameson

2023

Preprint

View full text Add to dashboard Cite

Klebsiellaspp. are causative agents of healthcare associated infections in patients who are immunocompromised and use medical devices. The antibiotic resistance crisis has led to an increase in infections caused by these bacteria, which can develop into potentially life-threatening illness if not treated swiftly and effectively. Thus, new treatment options forKlebsiellaare urgently required. Phage therapy can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria infections. The aim of the present study was to produce a safe and effective phage cocktail treatment againstK. pneumoniaeandK. oxytoca, both in liquidin vitroculture and anin vivo Galleria mellonellainfection model. The phage cocktail was significantly more effective at killingK. pneumoniaeandK. oxytocastrains compared with monophage treatments. Preliminary phage cocktail safety was demonstrated through application in thein vivo G. mellonellamodel: where the phage cocktail induced no toxic side effects inG. mellonella. In addition, the phage cocktail significantly improved the survival ofG. mellonellawhen administered as a prophylactic treatment, compared with controls. In conclusion, our phage cocktail was demonstrated to be safe and effective againstKlebsiellaspp. in theG. mellonellainfection model. This provides a strong case for future treatment forKlebsiellainfections, either as an alternative, or adjunct to, antibiotics.

show abstract

Section: Discussionsupporting

confidence: 78%

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

Kelly,

Jameson

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The method of optimal multiplicity of infection is similar to those described by Mingfang Pu et al. with slight changes ( Pu et al., 2022 ). Briefly, exponential host cells were mixed with the phages with different multiplicities of infection (MOI: 0.0001,0.001,0.01,0.1,1,10,100), then shaken for 12 h at 37°C (220 rpm).…”

Section: Methodsmentioning

confidence: 99%

“…The method of mouse experiments was performed as previously described by Mingfang Pu et al. with slight changes ( Pu et al., 2022 ). Briefly, 91 female specific-pathogen-free (SPF) BALB/c mice, aged 4-5 weeks and weighed 18-20 g, were purchased from Beijing Huafukang Biotechnology Co., Ltd. All animal experiments were followed National Guidelines for Experimental Animal Welfare (Ministry of Science and Technology of China) and approved by the Animal Welfare and Research Ethics Committee at Southwest Medical University (swmu20230036).…”

Section: Methodsmentioning

confidence: 99%

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

Fang,

Dai,

Xiang

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has driven us to explore alternative treatments for the limitation of antimicrobial agents. Lytic phages are considered a promising alternative treatment for CR-hvKP infection. In this study, we reported three novel lytic phages, vB_KpnA_SCNJ1-Z, vB_KpnS_SCNJ1-C, and vB_KpnM_SCNJ1-Y, against a CR-hvKP strain SCNJ1, and they possess genomes of double-stranded DNA with a size of 43,428 bp, 46,039 bp, and 50,360 bp, respectively. Phylogenetic analysis demonstrated that vB_KpnA_SCNJ1-Z belongs to the family Autographiviridae within the class Caudoviricetes, while vB_KpnS_SCNJ1-C and vB_KpnM_SCNJ1-Y are unclassified Caudoviricetes. The phages showed a narrow host range only lysing 1 of 50 tested clinical bacterial strains. The one-step growth curves and stability results showed that the phages displayed relatively short latency periods, with broad pH (pH 3-14) and thermal stabilities (20–60°C). The phages showed significant inhibition of the biofilm formation by SCNJ1 and strong antibacterial activity in vitro. In the mouse model, we demonstrated that administration of a single phage or phage cocktail significantly reduced bacteria loads in the lung, liver, and spleen, and effectively rescued mice from the infection of the SCNJ1 strain, with a survival rate of 70-80%. These findings suggested the three phages have great potential as an alternative therapy with favorable stability and strong antibacterial activity both in vivo and in vitro for the treatment of CR-hvKP infection.

show abstract

“…Some reports have proven the effectiveness of antibacterial phages against Klebsiella [ 13 , 14 ] . However, most studies on Klebsiella phages have focused predominantly on the K1, K2 and KL64 serotypes [ 15 , 16 ]. The evaluation of phage antibacterial properties against K5 K. pneumoniae remains scarce and limited to only one existing assessment [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection

Li,

Guo,

Zheng

et al. 2024

Vet Res

View full text Add to dashboard Cite

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

show abstract

Genomic characterization of a new phage BUCT541 against Klebsiella pneumoniae K1-ST23 and efficacy assessment in mouse and Galleria mellonella larvae

Abstract: and Fan H ( ) Genomic characterization of a new phage BUCT against Klebsiella pneumoniae K -ST and e cacy assessment in mouse and Galleria mellonella larvae.

Cited by 12 publications

References 57 publications

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

Bacteriophage cocktail shows no toxicity and improves the survival ofGalleria mellonellainfected withKlebsiellaspp.

Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection

Contact Info

Product

Resources

About