Antibacterial Activity of combinatorial treatments composed of transition-metal/antibiotics against Mycobacterium tuberculosis

Abstract

Notwithstanding evidence that tuberculosis (TB) is declining, one of the greatest concerns to public health is the emergence and spread of multi-drug resistant strains of Mycobacterium tuberculosis (MDR-TB). MDR-TB are defined as strains which are resistant to at least isoniazid (INH) and rifampicin, the two most potent TB drugs, and their increasing incidence is a serious concern. Recently, notable efforts have been spent on research to pursue novel treatments against MDR-TB, especially on synergistic drug combinations as they have the potential to improve TB treatment. Our research group has previously reported promising synergistic antimicrobial effects between transition-metal compounds and antibiotics in Gram-negative and Gram-positive bacteria. In this work, we evaluated antimycobacterial activity of transition-metals/antibiotics combinatorial treatments against first-line drug resistant strains of Mycobacterium tuberculosis . Our data showed that INH/AgNO 3 combinatorial treatment had an additive effect (bactericidal activity) in an isoniazid-resistant clinical strain of Mycobacterium tuberculosis . Moreover, in vitro evaluation of cytotoxicity induced by both, the individual tratments of AgNO 3 and INH and the combinatorial treatment of INH/AgNO 3 in murine RAW 264.7 macrophages and human A549 lung cells; showed no toxic effects. Together, this data suggests that the INH/AgNO 3 combinatorial treatment could be used in the development of new strategies to treat resistant strains of Mycobacterium tuberculosis .

Aminoglycoside 6′-N-acetyltransferase Type Ib [AAC(6′)-Ib]-Mediated Aminoglycoside Resistance: Phenotypic Conversion to Susceptibility by Silver Ions

“…Despite taking a backstage role after the advent of antibiotics, silver has been continuously used in different forms [1,2]. Furthermore, due to the multidrug resistance crisis, the utilization of silver as a component of combination therapies or other novel formulations has regained interest [3][4][5][6][7].…”

The Demand for New Antibiotics: Antimicrobial Peptides, Nanoparticles, and Combinatorial Therapies as Future Strategies in Antibacterial Agent Design

“…Combinatorial treatments composed of isoniazid/silver exhibited a synergistic bactericidal effect in an isoniazid-resistant clinical strain of M. tuberculosis (Montelongo-Peralta et al, 2019). Moreover, a previous study showed the ability of silver to potentiate the activity of a broad range of antibiotics against Gram-negative bacteria, as well as to restore antibiotic susceptibility (re-sensitizing) to a resistant bacterial strain (Morones-Ramirez et al, 2013).…”

“…Combinatorial treatments composed of isoniazid/silver exhibited a synergistic bactericidal effect in an isoniazid-resistant clinical strain of M . tuberculosis ( Montelongo-Peralta et al, 2019 ).…”

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy

“…One of the most widely used combinatorial formulations in clinical practice is amoxicillin with clavulanic acid, where amoxicillin is an inhibitor of peptidoglycan synthesis while clavulanic acid inhibits the β-lactamase enzyme which degrades amoxicillin ( Huttner et al., 2019 ). Similar approaches combine two molecules which each independently exhibit antimicrobial activity and combine the dosing for treatment ( Montelongo-Peralta et al., 2019 ; Opalski et al., 2020 ). Many of these combinations are designed such that the two antimicrobials act via different mechanisms, ideally each enhancing the activity of the other.…”