Mycobacterium smegmatis whmD and its homologue Mycobacterium tuberculosis whiB2 are functionally equivalent

Raghunand, Tirumalai R.; Bishai, William R.

doi:10.1099/mic.0.28911-0

Cited by 40 publications

(32 citation statements)

References 46 publications

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“…Instead, M. tuberculosis encodes a 7-member family of WhiB ironsulfur (Fe-S) cluster TFs that sense the redox state in the cell and regulate gene expression accordingly (92). Of these, whiB1 and whiB2 are predicted to be essential, although their regulons have yet to be defined (93)(94)(95). whiB1 is also upregulated during hypoxia and within infected mouse lungs (96,97).…”

Section: Essential Tcss and Tfs-always On The Lookout For Hostilitymentioning

confidence: 99%

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

2016

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Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress, M. tuberculosis is prepared for battle against the host defense and able to persist within the human population.T he survival of any organism relies on its ability to sense and respond to changes in its environment. For bacteria, stress responses are primarily mediated through the regulation of gene expression. By integrating multiple molecular approaches to gene regulation, pathogenic bacteria are able to orchestrate conditionspecific patterns that promote survival and pathogenesis in the face of a strong immune response. This minireview focuses on mechanisms of transcription regulation required for stress responses in one of the most successful and deadly pathogens in the world, Mycobacterium tuberculosis. M. tuberculosis has coexisted with humans for Ͼ50,000 years (1) and continues to cause more than 1.5 million deaths a year (2). The coevolution of M. tuberculosis with the human host response to infection has resulted in a pathogen that is specialized for long-term infection in people. Tuberculosis is a complex disease that requires the bacteria to multiply within phagocytes, survive extracellularly in hypoxic and necrotic granulomas, and endure a robust immune response to persist in the host. During infection, the host immune response restrains M. tuberculosis from proliferating by imposing a battery of defenses, including reactive oxygen and nitrogen stress, hypoxia, acid stress, genotoxic stress, cell surface stress, and starvation (3). Despite this onslaught of attacks, M. tuberculosis is able to persist for the lifetime of the host, indicating that this pathogen has highly effective molecular mechanisms to resist host-inflicted damage. In order to enact these defenses and facilitate this specialized lifestyle, M. tuberculosis executes a complex, interconnected web of stress responses that rely on changes in gene expression. In fact, M. tuberculosis is well suite...

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Section: Essential Tcss and Tfs-always On The Lookout For Hostilitymentioning

confidence: 99%

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

2016

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“…The M. tuberculosis putative transcription factor WhiB2 has been shown to be syntenous and functionally equivalent to WhmD of M. smegmatis (327). WhmD is also homologous to the S. coelicolor WhiB protein, which is not essential for growth but is required for proper aerial hyphae sporulation, where mutants fail to assemble Z rings and arrest without formation of septa (94).…”

Section: How Are Whib Proteins Involved In Growth Regulation?mentioning

confidence: 99%

Bacterial Growth and Cell Division: a Mycobacterial Perspective

Hett

Rubín

2008

Microbiol Mol Biol Rev

336

293

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SUMMARY The genus Mycobacterium is best known for its two major pathogenic species, M. tuberculosis and M. leprae, the causative agents of two of the world's oldest diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills approximately two million people each year and is thought to latently infect one-third of the world's population. One of the most remarkable features of the nonsporulating M. tuberculosis is its ability to remain dormant within an individual for decades before reactivating into active tuberculosis. Thus, control of cell division is a critical part of the disease. The mycobacterial cell wall has unique characteristics and is impermeable to a number of compounds, a feature in part responsible for inherent resistance to numerous drugs. The complexity of the cell wall represents a challenge to the organism, requiring specialized mechanisms to allow cell division to occur. Besides these mycobacterial specializations, all bacteria face some common challenges when they divide. First, they must maintain their normal architecture during and after cell division. In the case of mycobacteria, that means synthesizing the many layers of complex cell wall and maintaining their rod shape. Second, they need to coordinate synthesis and breakdown of cell wall components to maintain integrity throughout division. Finally, they need to regulate cell division in response to environmental stimuli. Here we discuss these challenges and the mechanisms that mycobacteria employ to meet them. Because these organisms are difficult to study, in many cases we extrapolate from information known for gram-negative bacteria or more closely related GC-rich gram-positive organisms.

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“…M. smegmatis WhmD is a homologue of WhiB, a Streptomyces coelicolor protein required for sporulation. Deficiency of these essential genes leads to a reduction in the frequency of septum formation and to the mycelial form of growth (Gomez & Bishai, 2000;Raghunand & Bishai, 2006 The measurement of cells from several mycobacterial species showed cell length variability, and the mean length of M. smegmatis mc 2 155 cells was determined to be 4.8 mm (Joyce et al, 2012). The mean width of mycobacterial cells is less variable (0.6 mm) (Wu et al, 2009;Nguyen et al, 2007); however, it can be significantly influenced by the cell wall composition (Wu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Morphological and proteomic analysis of early stage air–liquid interface biofilm formation in Mycobacterium smegmatis

et al. 2014

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We studied the early stages of pellicle formation by Mycobacterium smegmatis on the surface of a liquid medium [air-liquid interface (A-L)]. Using optical and scanning electron microscopy, we showed the formation of a compact biofilm pellicle from micro-colonies over a period of 8-30 h. The cells in the pellicle changed size and cell division pattern during this period. Based on our findings, we created a model of M. smegmatis A-L early pellicle formation showing the coordinate growth of cells in the micro-colonies and in the homogeneous film between them, where the accessibility to oxygen and nutrients is different. A proteomic approach utilizing high-resolution two-dimensional gel electrophoresis, in combination with mass spectrometry-based protein identification, was used to analyse the protein expression profiles of the different morphological stages of the pellicle. The proteins identified formed four expression groups; the most interesting of these groups contained the proteins with highest expression in the biofilm development phase, when the floating micro-colonies containing long and more robust cells associate into flocs and start to form a compact pellicle. The majority of these proteins, including GroEL1, are involved in cell wall synthesis or modification, mostly through the involvement of mycolic acid biosynthesis, and their expression maxima correlated with the changes in cell size and the rigidity of the bacterial cell wall observed by scanning electron microscopy.

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Mycobacterium smegmatis whmD and its homologue Mycobacterium tuberculosis whiB2 are functionally equivalent

Cited by 40 publications

References 46 publications

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

Bacterial Growth and Cell Division: a Mycobacterial Perspective

Morphological and proteomic analysis of early stage air–liquid interface biofilm formation in Mycobacterium smegmatis

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