Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis

Abstract

SUMMARY The Mycobacterium tuberculosis genome encodes five putative “alternative” ribosomal proteins whose expression is repressed at high Zn2+ concentration. Each alternative protein has a primary homolog that is predicted to bind Zn2+. We hypothesized that zinc triggers a switch between these paired homologous proteins and therefore chose one of these pairs, S18-1/S18-2, to study mechanisms of the predicted competition for their incorporation into ribosomes. As predicted, our data show that Zn2+-depletion causes accumulation of both S18-2 mRNA and protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under Zn2+-limited conditions. However the amount of S18-1 protein is markedly decreased. We further demonstrate that both S18 proteins interact with ribosomal protein S6, a committed step in ribosome biogenesis. Zn2+ is absolutely required for the S18-1/S6 interaction, while it is dispensable for S18-2/S6 dimer formation. These data suggest a model in which the S18-1 is the dominant ribosome constituent in high zinc conditions, e.g. inside of phagosomes, but that it can be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu. Consequently, Zn2+-depletion may serve as a signal for building alternative ribosomes when M. tuberculosis is released from macrophages, to allow survival in the extracellular environment.

Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112

“…For example, there was induction of pathways involved in mycobactin synthesis ( mbtB / C / D ), complex lipid phthiocerol dimycocerosate (PDIM) biosynthesis ( fadD26 , ppsA / B / C / D ), metabolism of alternative lipid carbon sources, the glyoxylate shunt ( icl ), the methylcitrate cycle ( prpD / C , prpR ) and triacylglycerol synthase ( tgs1 ). The isoniazid inducible genes ( iniB / A / C ) that respond to cell wall stress (Colangeli et al , ), and four of the nine genes coding for alternative ribosomal proteins, rpmB1 , rpmB2 , rpmG1 , rpsN2 (Prisic et al , ) were also induced.…”

Transcriptomes of the Extremely Thermoacidophilic Archaeon Metallosphaera sedula Exposed to Metal “Shock” Reveal Generic and Specific Metal Responses

“…The M. sedula genome contains 64 ORFs related to ribosomal proteins (78); 4 and 24 of them were uniquely downregulated by LD and HD Zn 2ϩ , respectively (see Table S1 in the supplemental material). M. sedula lacks identifiable paralogs of its primary suite of ribosomal proteins (78), indicating that the downregulation is not connected to the switching phenomenon observed in Mycobacterium tuberculosis (79) and Streptomyces coelicolor (80). Proper transcription of rRNA in E. coli requires the antitermination protein NusA (81), encoded by Msed_0037, which was downregulated by HD Zn 2ϩ .…”

Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association

“…While both clusters contain small and large subunit ribosomal proteins, each cluster is comprised of subsets of ribosomal genes and proteins specific to each type of cell culture (Table 1). Rather than representing a simple increase or decrease in ribosomal gene transcription levels, these cluster patterns are in all likelihood evidence of “ribosomal tuning” and differential usage of specific ribosomal proteins [29–32]. A comparison of I. hospitalis-N. equitans co-cultures to I. hospitalis- only cell cultures showed that 8 ribosomal protein mRNAs and 5 ribosomal proteins had fold changes greater than 10.…”

“…A comparable stress coping mechanism has been shown to occur in Mycobacterium tuberculosis [32]. In this case, the organism utilizes an alternate set of ribosomal proteins as a function of the availability of zinc [32].…”

“…A comparable stress coping mechanism has been shown to occur in Mycobacterium tuberculosis [32]. In this case, the organism utilizes an alternate set of ribosomal proteins as a function of the availability of zinc [32]. Other types of ribosomal protein tuning have been documented, whereby cells make adjustments to the levels, ratios, or types of ribosomal proteins in order to facilitate optimal growth as a function of changing nutrient availability [29–31].…”