Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a highly infectious disease and worldwide health problem. Based on the WHO TB report, 9 million active TB cases are emerging, leading to 2 million deaths each year. The recent emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains emphasizes the necessity to improve novel therapeutic plans. Among the various developing antibacterial approaches, phage therapy is thought to be a precise hopeful resolution. Mycobacteriophages are viruses that infect bacteria such as Mycobacterium spp., containing the M. tuberculosis complex. Phages and phage-derived proteins can act as promising antimicrobial agents. Also, phage cocktails can broaden the spectrum of lysis activity against bacteria. Recent researches have also shown the effective combination of antibiotics and phages to defeat the infective bacteria. There are limitations and concerns about phage therapy. For example, human immune response to phage therapy, transferring antibiotic resistance genes, emerging resistance to phages, and safety issues. So, in the present study, we introduced mycobacteriophages, their use as therapeutic agents, and their advantages and limitations as therapeutic applications.

Classification and characterisation of extracellular vesicles‐related tuberculosis subgroups and immune cell profiles

“…Infectious diseases such as TB are among the deadliest worldwide, with higher morbidity and mortality rates 25 . There is, however, a lack of understanding regarding the molecular factors that can contribute to negative TB patient outcomes.…”

Endolysin B as a new archetype inM. tuberculosistreatment

“…Additionally, the presence of this thick waxy layer further complicated mycobacteriophages, bacterial viruses selectively parasitizing mycobacteria, lysis 23 . Generally, bacteriophages encode within their genome only one peptidoglycan-degrading enzyme, namely endolysin A (LysA), which is essential in allowing bacteriophage extracellular propagation at the end of their lytic cycle 31,32 . Although the molecular mechanisms triggering peptidoglycan endolysins-mediated lysis are still poorly elucidated, the current model hypothesized that LysA starts to inertially accumulate at the inner membrane together with holins.…”

“…To overcome the complexity of the mycomembrane, mycobacteriophages release two different endolysins within the cytoplasm of their host, namely LysA and the mycolylarabinogalactan esterase endolysin B, LysB 12,13 . While LysA acts hydrolyzing the peptidoglycan layer, LysB cuts the ester link between the arabinogalactan and the mycolic acid disrupting mycobacterial integrity 32 . The concerted degrading action of both LysA and LysB finally leads to mycobacterial lysis, which occurs following the loss of communication between the bacillus cell wall the outer membrane 32 .…”

“…While LysA acts hydrolyzing the peptidoglycan layer, LysB cuts the ester link between the arabinogalactan and the mycolic acid disrupting mycobacterial integrity 32 . The concerted degrading action of both LysA and LysB finally leads to mycobacterial lysis, which occurs following the loss of communication between the bacillus cell wall the outer membrane 32 . Therefore, the endolysin-mediated lytic activity towards host bacteria, combined with the pressing need to counterbalance the exponential rise of antibiotic-resistant pathogens, are posing these lytic-derived enzymes as new potential antibacterial agents 18,23,32 .…”

“…To date, the two mostly investigated mycobacteriophage lysins are the Ms6-LysB FL and the D29-LysB 18,32 . Whereas recombinant D29-LysB appears to induce mycobacterial lysis and to disrupt biofilm 32 , Ms6-LysB FL only showed a growth-inhibitory effect when co-administered with a surfactant or with membrane-destabilizing cationic peptides 12,16,23,37 .…”