Evaluation of lytic bacteriophages for control of multidrug-resistant Salmonella Typhimurium

Abstract

BackgroundThe emergence of antibiotic-resistant bacteria can cause serious clinical and public health problems. This study describes the possibility of using bacteriophages as an alternative agent to control multidrug-resistant Salmonella Typhimurium.MethodsThe potential lytic bacteriophages (P22-B1, P22, PBST10, PBST13, PBST32, and PBST 35) were characterized by morphological property, heat and pH stability, optimum multiplicity of infection (MOI), and lytic activity against S. Typhimurium KCCM 40253, S. Typhimurium ATCC 19585, ciprofloxacin-induced antibiotic-resistant S. Typhimurium ATCC 19585, and S. Typhimurium CCARM 8009.ResultsP22-B1 and P22 belong to Podoviridae family and PBST10, PBST13, PBST32, and PBST 35 show a typical structure with polyhedral head and long tail, belonging to Siphoviridae family. Salmonella bacteriophages were highly stable at the temperatures (< 60 °C) and pHs (5.0–11.0). The reduction rates of host cells were increased at the MOI-dependent manner, showing the highest reduction rate at MOI of 10. The host cells were most effectively reduced by P22, while P22-B1 showed the least lytic activity. The ciprofloxacin-induced antibiotic-resistant S. Typhimurium ATCC 19585, and clinically isolated antibiotic-resistant S. Typhimurium CCARM 8009 were resistant to ciprofloxacin, levofloxacin, norfloxacin, and tetracycline. P22 showed the highest lytic activity against S. Typhimurium KCCM 40253 (> 5 log reduction), followed by S. Typhimurium ATCC 19585 (4 log reduction) and ciprofloxacin-induced antibiotic-resistant S. Typhimurium ATCC 19585 (4 log reduction).ConclusionThe results would provide vital insights into the application of lytic bacteriophages as an alternative therapeutics for the control of multidrug-resistant pathogens.

Bacteriophage activity against and characterisation of avian pathogenicEscherichia coliisolated from colibacillosis cases in Uganda

“…The effect of pH on phage viability at 25℃ and at 40℃ represented activity at room temperature and body temperature of chicken, respectively. The two phages were tolerant to a broad range of pH similar to what was observed in previous studies [26]. The tolerance to a broad range of temperature and pH coupled with a wide host range, makes the two phages suitable potential candidates for a cocktail product that can be used as an alternative to antibiotics in the control of APEC infections [27].…”

“…pH stability and thermal stability tests were carried out for the two phages with the broadest host ranges as described by Jung et al and Yu et al [26,27]. Briefly, the phages (10 8 PFU/ml) were incubated at different temperatures (20℃ to 70℃ ) for 30 mins.…”

Characterization of Tail Sheath Protein of N4-Like Phage phiAxp-3

“… Brackett et al (1997) demonstrated that a synthetic peptide corresponding to amino acid residues 20 through 44 of the neutrophil-derived 37-kDa cationic antimicrobial protein (CAP37 P20–44) can bind lipid A of LPS, which could be useful in attenuating in vivo responses induced during endotoxemia, including sepsis. The emergence of antibiotic-resistant bacteria can cause serious clinical and public health problems ( Jung et al, 2017 ). N4-like phages have been used as therapeutic agent in phage therapy against Pseudomonas aeruginosa infections and have been shown to be safe and effective ( Shigehisa et al, 2016 ).…”

Phage therapy for severe bacterial infections: a narrative review

“…However, phage clearance is also enhanced by the mammalian innate immune responses to infection — this may affect (or be affected by) amplification and/or phage dosage (the ratio of phages to bacteria; ie, the MOI). An MOI below 0.1 is effective in mouse models, but an optimal MOI to use in humans has been suggested to be ten or over . Bacterial concentrations are 10 1 –10 5 (more usually < 10 3 ) colony‐forming units per mL of blood in severe sepsis, and thus a dose of 10 9 plaque‐forming units (PFU) into the human blood volume (~ 5 L) is expected to yield an MOI input over 200.…”

“…An MOI below 0.1 is effective in mouse models, 47 but an optimal MOI to use in humans has been suggested to be ten or over. 48 Bacterial concentrations are 10 1 -10 5 (more usually < 10 3 ) colony-forming units per mL of blood in severe sepsis, 49 and thus a dose of 10 9 plaque-forming units (PFU) into the human blood volume (~ 5 L) is expected to yield an MOI input over 200.…”