Potential Drug Targets in Mycobacterial Cell Wall: Non-Lipid Perspective.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), still remains a deadly disease worldwide. With prolonged usage of anti-TB drugs, the current therapeutic regimes are becoming ineffective, particularly due to emergence of drug resistance in MTB. Under such compelling circumstances, it is pertinent to look for new drug targets. The cell wall envelope of MTB is composed of unique lipids that are frequently targeted for anti-TB therapy. This is evident from the fact that most of the commonly used front line drugs (Isoniazid and Ethambutol) act on lipid machinery of MTB. Thus, despite the fact that much of the attention is towards understanding the MTB lipid biology, in search for identification of new drug targets, our knowledge of bacterial cell wall non-lipid components remains rudimentary and underappreciated. Better understanding of such components of mycobacterial cell structure will help in the identification of new drug targets that can be utilized on the persistent mycobacterium. This review at a common platform summarizes some of the non-lipid cell wall components in MTB that have potential to be exploited as future drug targets.

Nonphotodynamic Roles of Methylene Blue: Display of Distinct Antimycobacterial and Anticandidal Mode of Actions.

Significance of methylene blue (MB) in photodynamic therapy against microbes is well established. Previously, we have reported the antifungal potential of MB against Candida albicans. The present study attempts to identify additional antimicrobial effect of MB against another prevalent human pathogen, Mycobacterium tuberculosis (MTB). We explored that MB is efficiently inhibiting the growth of Mycobacterium at 15.62 µg/ml albeit in bacteriostatic manner similar to its fungistatic nature. We uncovered additional cell surface phenotypes (colony morphology and cell sedimentation rate) which were impaired only in Mycobacterium. Mechanistic insights revealed that MB causes energy dependent membrane perturbation in both C. albicans and Mycobacterium. We also confirmed that MB leads to enhanced reactive oxygen species generation in both organisms that could be reversed upon antioxidant supplementation; however, DNA damage could only be observed in Mycobacterium. We provided evidence that although biofilm formation was disrupted in both organisms, cell adherence to human epithelial cells was inhibited only in Mycobacterium. Lastly, RT-PCR results showed good correlation with the biochemical assay. Together, apart from the well-established role of MB in photodynamic therapy, this study provides insights into the distinct antimicrobial mode of actions in two significant human pathogens, Candida and Mycobacterium, which can be extrapolated to improve our understanding of finding novel therapeutic options.

Multidrug resistance: an emerging crisis.

The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistance mechanisms and decrease in efficiency of treating common infectious diseases, it results in failure of microbial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as "super bugs." Although the development of MDR is a natural phenomenon, the inappropriate use of antimicrobial drugs, inadequate sanitary conditions, inappropriate food-handling, and poor infection prevention and control practices contribute to emergence of and encourage the further spread of MDR. Considering the significance of MDR, this paper, emphasizes the problems associated with MDR and the need to understand its significance and mechanisms to combat microbial infections.