Genome-wide transcription analyses in Mycobacterium tuberculosis treated with lupulone

Abstract

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, still causes higher mortality than any other bacterial pathogen until now. With the emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR-TB) strains, it becomes more important to search for alternative targets to develop new antimycobacterial drugs. Lupulone is a compound extracted from Hops (Hurnulus lupulus), which exhibits a good antimicrobial activity against M. tuberculosis with minimal inhibitory concentration (MIC) value of 10 μg/mL, but the response mechanisms of lupulone against M. tuberculosis are still poorly understood. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to MIC of lupulone. A total of 540 genes were found to be differentially regulated by lupulone. Of these, 254 genes were upregulated, and 286 genes were downregulated. A number of important genes were significantly regulated which are involved in various pathways, such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis. Real-time quantitative RT-PCR was performed for choosed genes to verified the microarray results. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis to a lupulone challenge.

Dissecting the Acid Stress Response of Rhizobium tropici CIAT 899

“…Furthermore, we identified a few putative transcription factors that might be implicated in the regulation of efflux pumps under acid stress (like DeoR, RTCIAT899_RS29995; TetR, RTCIAT899_RS10760, RTCIAT899_RS28830, or YebC/PmpR, RTCIAT899_RS14585). The TetR family of transcriptional regulators has been reported to be involved in the regulation of efflux pumps (Perrone et al, 2017 ) and drug efflux in mycobacteria (Betts et al, 2003 ; Wei et al, 2014 ). Among the DEGs that were up-regulated were also the hyc genes encoding hydrogenases proteins.…”

A Novel TetR-Like Transcriptional Regulator Is Induced in Acid-Nitrosative Stress and Controls Expression of an Efflux Pump in Mycobacteria

“…In addition to up-regulation by acid-nitrosative stress, Rv1687c/86c/85c have been shown to be induced upon exposure to triclosan and lupulone, compounds that show potential as anti-mycobacterial agents, therefore it is feasible to speculate that the TetR-regulated ABC transporter is involved in drug efflux ( Betts et al, 2003 ; Wei et al, 2014 ). A recent study, however, has shown that over-expression of Rv1686c-Rv1687c did not result in an increase in MIC to these compounds and further work is needed to investigate the role of this cluster in drug efflux ( Gomez et al, 2016 ).…”

Application of Omics Technologies for Evaluation of Antibacterial Mechanisms of Action of Plant-Derived Products

“…Generally, at least two different experimental situations are studied and the cDNA extracted from each is labeled with different fluorophores (Smith et al, 2005 ; Nagaraj and Singh, 2010 ). Microarrays have been used to elucidate the MOA of several phytochemicals, opening new insights into the modulation of different pathways caused by an antimicrobial agent (Hammami and Fliss, 2010 ; Chung et al, 2013 ; Wei et al, 2014 ; Eng and Nathan, 2015 ; Shen et al, 2015 ). We highlight some of them herein, with more examples provided in Table 1 .…”

“…Another example is a study carried out to evaluate the molecular effects triggered by lupulone (phenolic acid from Humulus lupulus ) in Mycobacterium tuberculosis . The authors reported that 540 genes were found to be differentially regulated, which were involved in various pathways such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis (Wei et al, 2014 ).…”