Posttranscriptional Regulation in Response to Different Environmental Stresses in Campylobacter jejuni

Li, Stephen; Lam, Jenna; Souliotis, Leonidas; Alam, Mohammad Tauqeer; Constantinidou, Chrystala

doi:10.1128/spectrum.00203-22

Cited by 3 publications

(3 citation statements)

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“…However, further investigation revealed extremely low RNAseq read counts of these transcripts occurred in all strains in our study, including WT. Expression of these genes has previously been shown to be increased during exposure to reactive oxygen species and is primarily under the control of several transcriptional regulators, including Fur, CosR, and PerR ( 19 , 44 , 45 ). As sRNA regulators are designed for fine-tuning of gene expression post-transcriptionally, if the primary transcriptional signal is not present, differences in mRNA stability cannot be detected.…”

Section: Discussionmentioning

confidence: 99%

“…More recent research has also identified two cis -encoded sRNAs that work together to regulate colonization factor ptmG ( 18 ). An additional sRNA has also recently been discovered that appears to regulate Tlps that transduce external stimuli to lead to a chemotactic response ( 19 ). Despite these advances, the roles sRNAs play in gene regulation in Campylobacter are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of Campylobacter jejuni

Ruddell

Hassall

Moss

et al. 2023

mBio

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Small non-coding RNAs (sRNAs) are important players in modulating gene expression in bacterial pathogens, but their functions are largely undetermined in Campylobacter jejuni , an important cause of foodborne gastroenteritis in humans. In this study, we elucidated the functions of sRNA CjNC140 and its interaction with CjNC110, a previously characterized sRNA involved in the regulation of several virulence phenotypes of C. jejuni . Inactivation of CjNC140 increased motility, autoagglutination, L-methionine concentration, autoinducer-2 production, hydrogen peroxide resistance, and early chicken colonization, indicating a primarily inhibitory role of CjNC140 for these phenotypes. Apart from motility, all these effects directly contrasted the previously demonstrated positive regulation by CjNC110, suggesting that CjNC110 and CjNC140 operate in an opposite manner to modulate physiologic processes in C. jejuni . RNAseq and northern blotting further demonstrated that expression of CjNC140 increased in the absence of CjNC110, while expression of CjNC110 decreased in the absence of CjNC140, suggesting a possibility of their direct interaction. Indeed, electrophoretic mobility shift assay demonstrated a direct binding between the two sRNAs via GA- (CjNC110) and CU- (CjNC140) rich stem-loops. Additionally, RNAseq and follow-up experiments identified that CjNC140 positively regulates p19 , which encodes a key iron uptake transporter in Campylobacter . Furthermore, computational analysis revealed both CjNC140 and CjNC110 are highly conserved in C. jejuni, and the predicted secondary structures support CjNC140 as a functional homolog of the iron regulatory sRNA, RyhB. These findings establish CjNC140 and CjNC110 as a key checks-and- balances mechanism in maintaining homeostasis of gene expression and optimizing phenotypes critical for C. jejuni pathobiology. IMPORTANCE Gene regulation is critical to all aspects of pathogenesis of bacterial disease, and small non-coding RNAs (sRNAs) represent a new frontier in gene regulation of bacteria. In Campylobacter jejuni , the role of sRNAs remains largely unexplored. Here, we investigate the role of two highly conserved sRNAs, CjNC110 and CjNC140, and demonstrate that CjNC140 displays a primarily inhibitory role in contrast to a primarily activating role for CjNC110 for several key virulence-associated phenotypes. Our results also revealed that the sRNA regulatory pathway is intertwined with the iron uptake system, another virulence mechanism critical for in vivo colonization. These findings open a new direction for understanding C. jejuni pathobiology and identify potential targets for intervention for this major foodborne pathogen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of Campylobacter jejuni

Ruddell

Hassall

Moss

et al. 2023

mBio

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“…Since post-transcriptional regulation is common in bacteria, including species closely related to C. jejuni [28,29], a proteomics approach (LC-MS/MS) was applied to detect proteins whose levels changed between analyzed strains or conditions. A total of 1170 proteins were detected (S1 Data); however, 173 proteins encoded by genes whose transcription changed in ΔCj1608 were not detected by MS ( S1 Data).…”

Section: Influence Of the Cj1608 Regulator On C Jejuni Gene And Prote...mentioning

confidence: 99%

CemR atypical response regulator impacts energy conversion inCampylobacteria

Noszka,

Strzałka,

Muraszko

et al. 2024

Preprint

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Campylobacter jejuni and Arcobacter butzleri are microaerobic food-borne human gastrointestinal pathogens that mainly cause diarrhoeal disease. These related species of the Campylobacteria class face variable atmospheric environments during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Thus, they need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonisation sites. Our studies revealed that C. jejuni and A. butzleri lacking a Campylobacteria-specific regulatory protein, C. jejuni Cj1608 or a homologue A. butzleri Abu0127, are unable to reprogram tricarboxylic acid cycle or respiration pathways, respectively, to produce ATP efficiently and, in consequence, adjust growth to changing oxygen supply. Based on these and previous studies on the homologous protein HP1021 in Helicobacter pylori, we propose that these regulatory proteins, which we named Campylobacteria energy and metabolism regulators (CemR), play an important role in Campylobacteria metabolism and energy regulation, allowing bacteria to adapt to variable oxygen availability.

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CemR atypical response regulator impacts energy conversion in Campylobacteria

Noszka,

Strzałka,

Muraszko

et al. 2024

mSystems

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Campylobacter jejuni and Arcobacter butzleri are microaerobic food-borne human gastrointestinal pathogens that mainly cause diarrheal disease. These related species of the Campylobacteria class face variable atmospheric environments during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Consequently, their lifestyles require that both pathogens need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonization sites. Our transcriptomic and proteomic studies revealed that C. jejuni and A. butzleri, lacking a Campylobacteria -specific regulatory protein, C. jejuni Cj1608, or a homolog, A. butzleri Abu0127, are unable to reprogram tricarboxylic acid cycle or respiration pathways, respectively, to produce ATP efficiently and, in consequence, adjust growth to changing oxygen supply. We propose that these Campylobacteria energy and metabolism regulators (CemRs) are long-sought transcription factors controlling the metabolic shift related to oxygen availability, essential for these bacteria’s survival and adaptation to the niches they inhabit. Besides their significant universal role in Campylobacteria , CemRs, as pleiotropic regulators, control the transcription of many genes, often specific to the species, under microaerophilic conditions and in response to oxidative stress. IMPORTANCE C. jejuni and A. butzleri are closely related pathogens that infect the human gastrointestinal tract. In order to infect humans successfully, they need to change their metabolism as nutrient and respiratory conditions change. A regulator called CemR has been identified, which helps them adapt their metabolism to changing conditions, particularly oxygen availability in the gastrointestinal tract so that they can produce enough energy for survival and spread. Without CemR, these bacteria, as well as a related species, Helicobacter pylori , produce less energy, grow more slowly, or, in the case of C. jejuni , do not grow at all. Furthermore, CemR is a global regulator that controls the synthesis of many genes in each species, potentially allowing them to adapt to their ecological niches as well as establish infection. Therefore, the identification of CemR opens new possibilities for studying the pathogenicity of C. jejuni and A. butzleri .

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Posttranscriptional Regulation in Response to Different Environmental Stresses in Campylobacter jejuni

Abstract: The foodborne pathogen C. jejuni is a significant challenge for the global health care system. It is crucial to investigate C. jejuni posttranscriptional regulation by small RNAs (sRNAs) in order to understand how it adapts to different stress conditions.

Cited by 3 publications

References 84 publications

Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of Campylobacter jejuni

Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of Campylobacter jejuni

CemR atypical response regulator impacts energy conversion inCampylobacteria

CemR atypical response regulator impacts energy conversion in Campylobacteria

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