ABSTRACT

   The survival strategies that Campylobacter jejuni (C. jejuni) employ
   throughout its transmission and infection life cycles remain largely
   elusive. Specifically, there is a lack of understanding about the
   posttranscriptional regulation of stress adaptations resulting from
   small noncoding RNAs (sRNAs). Published C. jejuni sRNAs have been
   discovered in specific conditions but with limited insights into their
   biological activities. Many more sRNAs are yet to be discovered as they
   may be condition-dependent. Here, we have generated transcriptomic data
   from 21 host- and transmission-relevant conditions. The data uncovered
   transcription start sites, expression patterns and posttranscriptional
   regulation during various stress conditions. This data set helped
   predict a list of putative sRNAs. We further explored the sRNAs’
   biological functions by integrating differential gene expression
   analysis, coexpression analysis, and genome-wide sRNA target
   prediction. The results showed that the C. jejuni gene expression was
   influenced primarily by nutrient deprivation and food storage
   conditions. Further exploration revealed a putative sRNA (CjSA21) that
   targeted tlp1 to 4 under food processing conditions. tlp1 to 4 are
   transcripts that encode methyl-accepting chemotaxis proteins (MCPs),
   which are responsible for chemosensing. These results suggested CjSA21
   inhibits chemotaxis and promotes survival under food processing
   conditions. This study presents the broader research community with a
   comprehensive data set and highlights a novel sRNA as a potential
   chemotaxis inhibitor.

   IMPORTANCE 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. However,
   limited data are available for investigating sRNA activity under
   stress. In this study, we generate gene expression data of C. jejuni
   under 21 stress conditions. Our data analysis indicates that one of the
   novel sRNAs mediates the adaptation to food processing conditions.
   Results from our work shed light on the posttranscriptional regulation
   of C. jejuni and identify an sRNA associated with food safety.

   KEYWORDS: C. jejuni, bioinformatics, sRNA, signal transduction,
   transcriptional regulation

INTRODUCTION

   Campylobacter jejuni (C. jejuni) is a leading foodborne pathogen that
   infects the gastrointestinal (GI) tract and causes inflammation,
   abdominal pain, fever, and diarrhea ([32]1[33]–[34]4). Occasionally,
   Campylobacter infection campylobacteriosis can lead to more severe
   complications such as reactive arthritis (RA), Guillain-Barre syndrome
   (GBS) and long-term childhood physical and cognitive impairments
   ([35]5[36]–[37]7).

   While C. jejuni is a fastidious organism to culture in the laboratory,
   its ability to adapt to stress during transmission makes it a
   successful pathogen. C. jejuni experiences environmental stresses such
   as but not limited to bile salt, temperature variations, reactive
   oxygen species (ROS), and host iron limitation ([38]8[39]–[40]10). It
   remains unclear how C. jejuni adapts to various environmental stresses
   with such a small genome (1.6 Mb) that carries only three annotated
   sigma factors and no conserved global stress response regulators like
   rpoS found in other Gram-negative bacteria ([41]11).

   Emerging evidence has brought to light the importance of sRNAs in
   stress response, infection, and antibiotic resistance ([42]12). sRNAs
   are short molecules ranging from 50 to 500 nucleotides that regulate
   biological processes by base-pairing with specific or multiple mRNA
   targets ([43]13[44]–[45]15). sRNAs can inhibit the translation of mRNA
   targets by physically blocking the ribosomal binding site (RBS)
   ([46]16, [47]17) or facilitating RNase E degradation
   ([48]18[49]–[50]20). sRNA-mRNA interactions can also activate
   translation initiation by disrupting secondary structures to expose the
   RBS ([51]21[52]–[53]23) or enhancing mRNA stability through inhibiting
   RNase E digestion ([54]24, [55]25). Examples of sRNA-mediated pathways
   include the tricarboxylic acid (TCA) cycle, amino acid uptake,
   oxidative stress response, iron homeostasis, virulence, and antibiotic
   resistance ([56]26[57]–[58]34).

   The lack of identified global RNA-binding proteins has hindered the
   discovery of C. jejuni sRNAs. There have been several published
   transcriptomic and RNA-Seq data sets ([59]35[60]–[61]39) that have
   enabled the detection of potential novel sRNAs in C. jejuni. Of these,
   references Dugar et al. ([62]35) and Porcelli et al. ([63]36) focused