<p>Phage therapy as a renewed therapeutic approach to mycobacterial infections: a comprehensive review</p>

Abstract

Mycobacterial infections are considered to a serious challenge of medicine, and the emergence of MDR and XDR tuberculosis is a serious public health problem. Tuberculosis can cause high morbidity and mortality around the world, particularly in developing countries. The emergence of drug-resistant Mycobacterium infection following limited therapeutic technologies coupled with the serious worldwide tuberculosis epidemic has adversely affected control programs, thus necessitating the study of the role bacteriophages in the treatment of mycobacterial infection. Bacteriophages are viruses that are isolated from several ecological specimens and do not exert adverse effects on patients. Phage therapy can be considered as a significant alternative to antibiotics for treating MDR and XDR mycobacterial infections. The useful ability of bacteriophages to kill Mycobacterium spp has been explored by numerous research studies that have attempted to investigate the phage therapy as a novel therapeutic/diagnosis approach to mycobacterial infections. However, there are restricted data about phage therapy for treating mycobacterial infections. This review presents comprehensive data about phage therapy in the treatment of mycobacterial infection, specifically tuberculosis disease.

Looking beyond Typical Treatments for Atypical Mycobacteria

“…Although still with limitations [178], the use of bacteriophages has several potential advantages, not only as an alternative to conventional antibiotics, but also by working synergistically with them [179]. The fact that they are highly specific on a species or even serovar level makes phages unable to infect host cells, causing no harm to the patient [178,179]. As bacteriophages replicate inside the bacteria, the administered dose can be very low [178].…”

“…The fact that they are highly specific on a species or even serovar level makes phages unable to infect host cells, causing no harm to the patient [178,179]. As bacteriophages replicate inside the bacteria, the administered dose can be very low [178]. Besides that, their mode-of-action is much faster than that of antibiotics, and their action is not dependent on the bacterial metabolic state [179].…”

“…Bacteriophages are unable to penetrate eukaryotic cell membranes; thus, in the case of intracellular pathogens such as NTM, delivery systems are needed to give them access to the infection sites [178]. Liposomes have been used to carry bacteriophages into infected host cells.…”

“…As an example, Neith et al [180] successfully delivered the mycobacteriophage TM4 inside giant liposomes into monocytic THP-1 cells. In many studies, the nonvirulent species of mycobacteria M. smegmatis was used as a mycobacteriophage delivery system [181][182][183], since it naturally infects phagocytic cells that host virulent mycobacteria, while allowing, at the same time, the proliferation of the phages inside them [178]. The mycobacteriophage TM4 was effective against M. avium and Mtb in vitro [182] and in vivo [183], significantly reducing the number of bacilli.…”

“…Broxmeyer et al [182] also proved that the vacuoles containing M. smegmatis carrying TM4 fuse with M. avium-containing vacuoles in the macrophage, potentiating the effect of the mycobacteriophage. TM4 is only one example among more than 4200 bacteriophages known to infect mycobacteria [178]. More studies need to be carried out with NTM in order to understand which bacteriophages can infect each type of mycobacteria and their mechanism of action.…”