Isolation of a bacteriophage targeting Pseudomonas aeruginosa and exhibits a promising in vivo efficacy

Abstract

Pseudomonas aeruginosa is an important pathogen that causes serious infections. Bacterial biofilms are highly resistant and render bacterial treatment very difficult, therefore necessitates alternative antibacterial strategies. Phage therapy has been recently regarded as a potential therapeutic option for treatment of bacterial infections. In the current study, a novel podovirus vB_PaeP_PS28 has been isolated from sewage with higher lytic activity against P. aeruginosa. Isolated phage exhibits a short latent period, large burst size and higher stability over a wide range of temperatures and pH. The genome of vB_PaeP_PS28 consists of 72,283 bp circular double-stranded DNA, with G + C content of 54.75%. The phage genome contains 94 open reading frames (ORFs); 32 for known functional proteins and 62 for hypothetical proteins and no tRNA genes. The phage vB_PaeP_PS28 effectively inhibited the growth of P. aeruginosa planktonic cells and displayed a higher biofilm degrading capability. Moreover, therapeutic efficacy of isolated phage was evaluated in vivo using mice infection model. Interestingly, survival of mice infected with P. aeruginosa was significantly enhanced upon treatment with vB_PaeP_PS28. Furthermore, the bacterial load in liver and kidney isolated from mice infected with P. aeruginosa and treated with phage markedly decreased as compared with phage-untreated P. aeruginosa-infected mice. These findings support the efficacy of isolated phage vB_PaeP_PS28 in reducing P. aeruginosa colonization and pathogenesis in host. Importantly, the isolated phage vB_PaeP_PS28 could be applied alone or as combination therapy with other lytic phages as phage cocktail therapy or with antibiotics to limit infections caused by P. aeruginosa.

Isolation of Streptococcus mutans temperate bacteriophage with broad killing activity to S. mutans clinical isolates

“…The one-step growth curve assay of φKSM96 was performed with the method described elsewhere. 43 φKSM96 (2 × 10 10 particles) was added to 2 mL of S. mutans KSM193 at exponential phase (OD660 nm of 0.2) and incubated for 30 min at 37°C with 5% CO 2. Then, bacterial cells were collected by the centrifugation at 10,000xg for 1 min.…”

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination

“…In numerous in vitro biofilm studies, phages have shown their efficacy in penetrating established biofilms and eradicating bacteria [ 321 ], and the effectiveness of single phages and phage cocktails to infect and lyse bacterial cells in single and multispecies biofilms has been confirmed [ 314 , 315 , 316 , 322 ]. Recent reports found that phages are highly effective at in vitro reducing and controlling bacterial biofilms, particularly those formed by S. aureus , K. pneumoniae , Acinetobacter baumannii , P. aeruginosa , Listeria monocytogenes , Salmonella sp., and E. coli [ 40 , 323 , 324 , 325 , 326 ]. For example, Peng et al [ 327 ] demonstrated that phage ɸMR003 displayed a broad host range against methicillin-resistant S. aureus of human origin.…”

“…QQ is a promising non-antibiotic alternative for the treatment of a broad range of pathogenic bacterial infections, including QQ enzymes, which inactivate QS signals, and QS inhibitors (QSIs), which chemically disrupt QS pathways via inhibition of signal receptors [ 33 , 35 ]. Moreover, several other innovative therapeutic strategies, like antimicrobial peptides [ 36 ], antibodies [ 37 ], nanoparticles [ 38 ], probiotics [ 39 ], and phage therapy [ 40 ], as well as precision genome targeting [ 41 ], aimed at effectively eradicating biofilm-related infections, are currently under investigation. Despite tremendous progress in antibiotic-resistant mechanisms and corresponding strategies to override resistance, biofilm-associated infections remain a considerable challenge.…”

Modulating Pseudomonas aeruginosa virulence by the anti-cholesterol drugs Atorvastatin and Rosuvastatin

“…Due to the notable increase in antimicrobial resistance rates, ongoing research is focusing on exploring new approaches and therapies beyond conventional antibiotics. These approaches include: using bacteriophages, monoclonal antibodies, antimicrobial peptides [13,14]. In addition to the use of antibiotic adjuvants to restore antibiotic activity such as e ux pump inhibitors and enzyme inhibitors [15,16].…”