Iron-regulated small RNA expression as Neisseria gonorrhoeae FA 1090 transitions into stationary phase growth

Abstract

BackgroundFor most pathogens, iron (Fe) homeostasis is crucial for maintenance within the host and the ability to cause disease. The primary transcriptional regulator that controls intracellular Fe levels is the Fur (ferric uptake regulator) protein, which exerts its action on transcription by binding to a promoter-proximal sequence termed the Fur box. Fur-regulated transcriptional responses are often fine-tuned at the post-transcriptional level through the action of small regulatory RNAs (sRNAs). Consequently, identifying sRNAs contributing to the control of Fe homeostasis is important for understanding the Fur-controlled bacterial Fe-response network.ResultsIn this study, we sequenced size-selected directional libraries representing sRNA samples from Neisseria gonorrhoeae strain FA 1090, and examined the Fe- and temporal regulation of these sRNAs. RNA-seq data for all time points identified a pool of at least 340 potential sRNAs. Differential analysis demonstrated that expression appeared to be regulated by Fe availability for at least fifteen of these sRNAs. Fourteen sRNAs were induced in high Fe conditions, consisting of both cis and trans sRNAs, some of which are predicted to control expression of a known virulence factor, and one SAM riboswitch. An additional putative cis-acting sRNA was repressed by Fe availability. In the pathogenic Neisseria species, one sRNA that contributes to Fe-regulated post-transcriptional control is the Fur-repressible sRNA NrrF. The expression of five Fe-induced sRNAs appeared to be at least partially controlled by NrrF, while the remainder was expressed independently of NrrF. The expression of the 14 Fe-induced sRNAs also exhibited temporal control, as their expression levels increased dramatically as the bacteria entered stationary phase.ConclusionsHere we report the temporal expression of Fe-regulated sRNAs in N. gonorrhoeae FA 1090 with several appearing to be controlled by the Fe-repressible sRNA NrrF. Temporal regulation of these sRNAs suggests a regulatory role in controlling functions necessary for survival, and may be important for phenotypes often associated with altered growth rates, such as biofilm formation or intracellular survival. Future functional studies will be needed to understand how these regulatory sRNAs contribute to gonococcal biology and pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3684-8) contains supplementary material, which is available to authorized users.

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

“…Putative small RNAs (sRNAs: defined as expression representing an intergenic region of the complementary strand of a known open reading frame [ORF] and 30 to 250 nucleotides in length) were also regulated during infection; 29 sRNAs were increased in vivo compared to in vitro , and 21 sRNAs were decreased in vivo (see Table S6 in Data Set S1 ). Among these sRNAs, several have been described previously ( 48 , 49 ).…”

Iron Deficiency Generates Oxidative Stress and Activation of the SOS Response in Caulobacter crescentus

“…Iron-bound Fur acts as transcriptional repressor under iron sufficient conditions, inhibiting the expression of genes for iron uptake and for non-essential iron enzymes ( Andrews et al, 2003 ; Lee and Helmann, 2007 ). In several bacteria the repression by iron-Fur is released under iron limitation, allowing the expression of a small RNA (called RyhB in Escherichia coli , FsrA in Bacillus subtilis, PrrF1 and PrrF2 in Pseudomonas aeruginosa , NrrF in Neisseria meningitidis, and Bc_KC_sr1 and Bc_KC_sr2 in Burkholderia cenocepacia KC-01), which facilitates the degradation of the mRNA of non-essential iron enzymes ( Masse and Gottesman, 2002 ; Wilderman et al, 2004 ; Masse et al, 2005 , 2007 ; Mellin et al, 2007 ; Gaballa et al, 2008 ; Ghosh et al, 2017 ; Jackson et al, 2017 ).…”

The Combined Effect of Cold and Copper Stresses on the Proliferation and Transcriptional Response of Listeria monocytogenes

“…On the contrary, cop A (heavy metal-transporting ATPase) transcription levels were similar in both temperatures tested. This discrepancy between expression levels and the intracellular copper content might be due to the activation of some post-transcriptional mechanisms that may be affecting transcript stability at 8°C, consequently reducing the translation of those proteins (Horn et al, 2007; Saberi et al, 2016; Jackson et al, 2017). These mechanisms may explain differences in intracellular copper content observed when growing L. monocytogenes at different temperatures.…”