Applications of bacteriophages against intracellular bacteria

Abstract

Infectious diseases pose a significant threat to both human and animal populations. Intracellular bacteria are a group of pathogens that invade and survive within the interior of eukaryotic cells, which in turn protect them from antibacterial drugs and the host immune system. Limited penetration of antibacterials into host cells results in insufficient bacterial clearance and treatment failure. Bacteriophages have, over the decades, been proved to play an important role in combating bacterial infections (phage therapy), making them an important alternative to classical antibiotic strategies today. Phages have been found to be effective at killing various species of extracellular bacteria, but little is still known about how phages control intracellular infections. With advances in phage genomics and mechanisms of delivery and cell uptake, the development of phagebased antibacterial strategies to address the treatment of intracellular bacteria has general potential. In this review, we present the current state of knowledge regarding the application of bacteriophages against intracellular bacteria. We cover phage deployment against the most common intracellular pathogens with special attention to therapeutic and preventive strategies.

A novel lytic phage potentially effective for phage therapy against Burkholderia pseudomallei in the tropics

“…A completely different approach to the treatment of bacterial infections, employing bacteriophages, viruses that specifically infect bacteria, is one potential way of circumventing the problems of antibiotic resistance [ 14 ]. Phages with activity against B .…”

“…A completely different approach to the treatment of bacterial infections, employing bacteriophages, viruses that specifically infect bacteria, is one potential way of circumventing the problems of antibiotic resistance [14]. Phages with activity against B. pseudomallei were described as early as the 1950s, when they were successfully isolated from the aquatic environment in Vietnam [15].…”

Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection

“…111 Current reviews regarding the application of bacteriophages against intracellular bacteria have also been reported. 112,113 Benefit from progress of phage genomics and nano-functionalization technology, the specificity and infectivity of phage are improving. Developing strategies combined with nanocarriers and bacteriophages to improve the treatment of intracellular bacterial infections has great potential.…”

Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial

“…7 The Biostatistics Center, The George Washington University, Rockville, MD, USA. 8 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA. 9 Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.…”

“…Unique features that make phages attractive for clinical use include their bactericidal activity [ 4 , 8 ], high specificity for target pathogens including MDRGN organisms [ 8 ], the ability to penetrate eukaryotic cells and target intracellular bacteria [ 8 ], amplification in vivo in the presence of target bacteria [ 9 ], biofilm penetration and antibiofilm activity [ 10 ], avoidance of host tissue damage [ 8 , 9 ], preservation of the human microbiome (compared with antibiotics) [ 11 ], and frequent synergy with antibiotics [ 12 ]. However, rigorous scientific investigations are required to address critical gaps in knowledge before phage therapy can be routinely used in clinical practice.…”