Identification of idiosyncratic<i>Mycobacterium tuberculosis</i>ribosomal protein subunits with implications in extraribosomal function, persistence, and drug resistance based on transcriptome data

Fan, Xiangyu; Tang, Xiemei; Yan, Jianlong; Xie, Jianping

doi:10.1080/07391102.2013.826143

Cited by 6 publications

(4 citation statements)

References 12 publications

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“…The gene rv1405c codes for a virulence associated methyltransferase that plays a role during the adaptation of M.tb to acidic stress ( Healy et al, 2016 ). The gene rv2057c encodes a ribosomal protein which is mainly involved in protein synthesis but have been suggested to play other physiological roles ( Fan et al, 2014 ). The gene rv1057 codes for a protein that belongs to a structurally distinct group of proteins known as β-propellers ( Haydel and Clark-Curtiss, 2006 ) and plays a role in the secretion of the virulence factor ESAT-6 ( Fu et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

The efflux pumps Rv1877 and Rv0191 play differential roles in the protection of Mycobacterium tuberculosis against chemical stress

Sao Emani,

Reiling

2024

Front. Microbiol.

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BackgroundIt was previously shown that GlnA3sc enabled Streptomyces coelicolor to survive in excess polyamines. However, subsequent studies revealed that Rv1878, the corresponding Mycobacterium tuberculosis (M.tb) ortholog, was not essential for the detoxification of spermine (Spm), in M.tb. On the other hand, the multi-drug efflux pump Rv1877 was previously shown to enable export of a wide range of compounds, while Rv0191 was shown to be more specific to chloramphenicol.RationaleTherefore, we first wanted to determine if detoxification of Spm by efflux can be achieved by any efflux pump, or if that was dependent upon the function of the pump. Next, since Rv1878 was found not to be essential for the detoxification of Spm, we sought to follow-up on the investigation of the physiological role of Rv1878 along with Rv1877 and Rv0191.ApproachTo evaluate the specificity of efflux pumps in the mycobacterial tolerance to Spm, we generated unmarked ∆rv1877 and ∆rv0191 M.tb mutants and evaluated their susceptibility to Spm. To follow up on the investigation of any other physiological roles they may have, we characterized them along with the ∆rv1878 M.tb mutant.ResultsThe ∆rv1877 mutant was sensitive to Spm stress, while the ∆rv0191 mutant was not. On the other hand, the ∆rv1878 mutant grew better than the wild-type during iron starvation yet was sensitive to cell wall stress. The proteins Rv1877 and Rv1878 seemed to play physiological roles during hypoxia and acidic stress. Lastly, the ∆rv0191 mutant was the only mutant that was sensitive to oxidative stress.ConclusionThe multidrug MFS-type efflux pump Rv1877 is required for Spm detoxification, as opposed to Rv0191 which seems to play a more specific role. Moreover, Rv1878 seems to play a role in the regulation of iron homeostasis and the reconstitution of the cell wall of M.tb. On the other hand, the sensitivity of the ∆rv0191 mutant to oxidative stress, suggests that Rv0191 may be responsible for the transport of low molecular weight thiols.

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Section: Resultsmentioning

confidence: 99%

The efflux pumps Rv1877 and Rv0191 play differential roles in the protection of Mycobacterium tuberculosis against chemical stress

Sao Emani,

Reiling

2024

Front. Microbiol.

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“…Certain r-proteins have been reported as having extra-ribosomal functions relating to various biological processes or functions in mammals (29,30), yeast (31)(32)(33), and bacteria (3,4,34). However, there are some functions of r-proteins unrelated to ribosome function that remain to be determined (2,3,35).…”

Section: Discussionmentioning

confidence: 99%

Posttranscriptional Regulation of tnaA by Protein-RNA Interaction Mediated by Ribosomal Protein L4 in Escherichia coli

2020

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Escherichia coli ribosomal protein (r-protein) L4 has extraribosomal biological functions. Previously, we described L4 as inhibiting RNase E activity through protein-protein interactions. Here, we report that from stabilized transcripts regulated by L4-RNase E, mRNA levels of tnaA (encoding tryptophanase from the tnaCAB operon) increased upon ectopic L4 expression, whereas TnaA protein levels decreased. However, at nonpermissive temperatures (to inactivate RNase E), tnaA mRNA and protein levels both increased in an rne temperature-sensitive [rne(Ts)] mutant strain. Thus, L4 protein fine-tunes TnaA protein levels independently of its inhibition of RNase E. We demonstrate that ectopically expressed L4 binds with transcribed spacer RNA between tnaC and tnaA and downregulates TnaA translation. We found that deletion of the 5′ or 3′ half of the spacer compared to the wild type resulted in a similar reduction in TnaA translation in the presence of L4. In vitro binding of L4 to the tnaC-tnaA transcribed spacer RNA results in changes to its secondary structure. We reveal that during early stationary-phase bacterial growth, steady-state levels of tnaA mRNA increased but TnaA protein levels decreased. We further confirm that endogenous L4 binds to tnaC-tnaA transcribed spacer RNA in cells at early stationary phase. Our results reveal the novel function of L4 in fine-tuning TnaA protein levels during cell growth and demonstrate that r-protein L4 acts as a translation regulator outside the ribosome and its own operon. IMPORTANCE Some ribosomal proteins have extraribosomal functions in addition to ribosome translation function. The extraribosomal functions of several r-proteins control operon expression by binding to own-operon transcripts. Previously, we discovered a posttranscriptional, RNase E-dependent regulatory role for r-protein L4 in the stabilization of stress-responsive transcripts. Here, we found an additional extraribosomal function for L4 in regulating the tna operon by L4-intergenic spacer mRNA interactions. L4 binds to the transcribed spacer RNA between tnaC and tnaA and alters the structural conformation of the spacer RNA, thereby reducing the translation of TnaA. Our study establishes a previously unknown L4-mediated mechanism for regulating gene expression, suggesting that bacterial cells have multiple strategies for controlling levels of tryptophanase in response to varied cell growth conditions.

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“…Moreover, RP-L33 was demonstrated to be a core member of the minimal set of bacterial genes which is essential to maintain cell life 25 . RP-L33 was suggested as the putative drug target in three Streptococcus species ( S. agalactiae , S. pneumoniae , and S. pyogenes ) 26 , two Bordetella species ( B. pertussis and B. parapertussis ) 27 , Helicobacter pylori 28 and Mycobacterium tuberculosis 29 .…”

Section: Discussionmentioning

confidence: 99%

Discrimination of contagious and environmental strains of Streptococcus uberis in dairy herds by means of mass spectrometry and machine-learning

Esener

Green

Emes

et al. 2018

Sci Rep

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Streptococcus uberis is one of the most common pathogens of clinical mastitis in the dairy industry. Knowledge of pathogen transmission route is essential for the selection of the most suitable intervention. Here we show that spectral profiles acquired from clinical isolates using matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) can be used to implement diagnostic classifiers based on machine learning for the successful discrimination of environmental and contagious S. uberis strains. Classifiers dedicated to individual farms achieved up to 97.81% accuracy at cross-validation when using a genetic algorithm, with Cohen’s kappa coefficient of 0.94. This indicates the potential of the proposed methodology to successfully support screening at the herd level. A global classifier developed on merged data from 19 farms achieved 95.88% accuracy at cross-validation (kappa 0.93) and 70.67% accuracy at external validation (kappa 0.34), using data from another 10 farms left as holdout. This indicates that more work is needed to develop a screening solution successful at the population level. Significant MALDI-TOF spectral peaks were extracted from the trained classifiers. The peaks were found to correspond to bacteriocin and ribosomal proteins, suggesting that immunity, growth and competition over nutrients may be correlated to the different transmission routes.

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Identification of idiosyncraticMycobacterium tuberculosisribosomal protein subunits with implications in extraribosomal function, persistence, and drug resistance based on transcriptome data

Cited by 6 publications

References 12 publications

The efflux pumps Rv1877 and Rv0191 play differential roles in the protection of Mycobacterium tuberculosis against chemical stress

The efflux pumps Rv1877 and Rv0191 play differential roles in the protection of Mycobacterium tuberculosis against chemical stress

Posttranscriptional Regulation of tnaA by Protein-RNA Interaction Mediated by Ribosomal Protein L4 in Escherichia coli

Discrimination of contagious and environmental strains of Streptococcus uberis in dairy herds by means of mass spectrometry and machine-learning

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