Antimycobacterial Potential of Mycobacteriophage Under Disease-Mimicking Conditions.

Yeswanth Chakravarthy Kalapala,Rachit Agarwal,Pallavi Raj Sharma

doi:10.3389/fmicb.2020.583661

Yeswanth Chakravarthy Kalapala, Rachit Agarwal + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2020.583661

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Abstract

Antibiotic resistance continues to be a major global health risk with an increase in multi-drug resistant infections seen across nearly all bacterial diseases. Mycobacterial infections such as Tuberculosis (TB) and Non-Tuberculosis infections have seen a significant increase in the incidence of multi-drug resistant and extensively drug-resistant infections. With this increase in drug-resistant Mycobacteria, mycobacteriophage therapy offers a promising alternative. However, a comprehensive study on the infection dynamics of mycobacteriophage against their host bacteria and the evolution of bacteriophage (phage) resistance in the bacteria remains elusive. We aim to study the infection dynamics of a phage cocktail against Mycobacteria under various pathophysiological conditions such as low pH, low growth rate and hypoxia. We show that mycobacteriophages are effective against M. smegmatis under various conditions and the phage cocktail prevents emergence of resistance for long durations. Although the phages are able to amplify after infection, the initial multiplicity of infection plays an important role in reducing the bacterial growth and prolonging efficacy. Mycobacteriophages are effective against antibiotic-resistant strains of Mycobacterium and show synergy with antibiotics such as rifampicin and isoniazid. Finally, we also show that mycobacteriophages are efficient against M. tuberculosis both under lag and log phase for several weeks. These findings have important implications for developing phage therapy for Mycobacterium.

Highlights

Prolonged and unsupervised use of antibiotics results in an increase of antibiotic resistance across all bacterial species which is considered a major threat to human health (Keshavjee and Farmer, 2012; Sprenger and Fukuda, 2016)
We show that mycobacteriophage cocktails are effective against Mycobacterium under the low pH, hypoxic and stationary conditions and showed synergy with antibiotics
In order to test their efficacy, M. smegmatis bacterial cultures were infected with phages at the Multiplicity of Infection (MOI) of 10 either in the lag phase or in the mid-log phase

Summary

Introduction

Prolonged and unsupervised use of antibiotics results in an increase of antibiotic resistance across all bacterial species which is considered a major threat to human health (Keshavjee and Farmer, 2012; Sprenger and Fukuda, 2016). The Mycobacterium genus with over 190 recognized species contains various pathogenic species including M. tuberculosis, M. leprae, M. abscessus, and M. avium complex, etc. In order to tackle this growing rate of antibiotic resistance and the side effects of antibiotic treatment regimens, various therapeutic strategies have been proposed, including phage therapy, that has shown tremendous potential against various bacterial pathogens (Kortright et al, 2019)

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