Small RNAs in mycobacteria: an unfolding story

Haning, Katie; Cho, Seung Hee; Contreras, Lydia M.

doi:10.3389/fcimb.2014.00096

Cited by 50 publications

(56 citation statements)

References 92 publications

(109 reference statements)

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“…To date, these genomic features have not been included in TnSeq analyses because they contain only a few TA sites. In addition, there has been little consensus between studies describing the identification of sRNAs and their boundaries (42–45). …”

Section: Resultsmentioning

confidence: 99%

Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis

DeJesus

Gerrick

et al. 2017

mBio

527

708

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For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed. We sought to overcome this limitation by creating a completely saturated transposon library in Mycobacterium tuberculosis. In assessing the composition of this highly saturated library by deep sequencing, we discovered that a previously unknown sequence bias of the Himar1 element rendered approximately 9% of potential TA dinucleotide insertion sites less permissible for insertion. We used a hidden Markov model of essentiality that accounted for this unanticipated bias, allowing us to confidently evaluate the essentiality of features that contained as few as 2 TA sites, including open reading frames (ORF), experimentally identified noncoding RNAs, methylation sites, and promoters. In addition, several essential regions that did not correspond to known features were identified, suggesting uncharacterized functions that are necessary for growth. This work provides an authoritative catalog of essential regions of the M. tuberculosis genome and a statistical framework for applying saturating mutagenesis to other bacteria.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis

DeJesus

Gerrick

et al. 2017

mBio

527

708

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“…In particular, there is a growing area of research into the roles of nucleoid-associated proteins and small RNAs (150)(151)(152)(153)(154)(155). M. tuberculosis also contains 11 serine/ threonine protein kinases (STPKs) that, like TCSs, are involved in signal transduction pathways that aid M. tuberculosis in adaptation to its environment (156 …”

Section: Final Thoughtsmentioning

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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“…The applicability of such sRNAs to other bacteria species still remains unclear and should be elucidated (Irnov et al, 2010). However, sRNAs have been discovered in many other microorganisms including Bacillus species, Clostridium species, Deinococcus radiodurans, Lactobacillus rhamnosus, Listeria monocytogenes, Mycobacterium species, Pseudomonas aeruginosa, Staphylococcus aureus, Streptomyces, Synechocystis PCC6803 and Zymomonas mobilis (Bouazzaoui and LaPointe, 2006;Cho et al, 2014;Christiansen et al, 2006;Desai and Papoutsakis, 1999;Duhring et al, 2006;Geissmann et al, 2009;Haning et al, 2014;Kaur et al, 2009;Sonnleitner et al, 2012;Tsai et al, 2015), and they are evolutionarily well-conserved. Therefore, synthetic sRNAs developed in other species may also function in Bacillus.…”

Section: Engineering Bacillus Using Ncrnasmentioning

confidence: 98%

Rapid and high-throughput construction of microbial cell-factories with regulatory noncoding RNAs

Chaudhary

Lee

2015

Biotechnology Advances

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Small RNAs in mycobacteria: an unfolding story

Cited by 50 publications

References 92 publications

Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis

Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

Rapid and high-throughput construction of microbial cell-factories with regulatory noncoding RNAs

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