The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni

Johnson, Jeff S.; Gaddy, Jennifer A.; DiRita, Victor J.

doi:10.1128/mbio.01691-16

Cited by 19 publications

(20 citation statements)

References 41 publications

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“…1d ). chuA is not required for chicken colonization 26 and is modestly upregulated in the chick cecum (<10 fold increase in vivo ), although it is highly upregulated in human infection samples (>1000 fold increase in vivo ). There are 161 genes that are differentially regulated specifically in our human samples and not in the chick cecum ( Fig.…”

Section: Campylobacter Gene Expression In Human Infection Samplesmentioning

confidence: 98%

Campylobacter jejuni transcriptional and genetic adaptation during human infection

et al. 2018

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Campylobacter jejuni infections are a leading cause bacterial food-borne diarrheal illness worldwide, and Campylobacter infections in children are associated with stunted growth and therefore long-term deficits into adulthood. Despite this global impact on health and human capital, how zoonotic C. jejuni responds to the human host remains unclear. Unlike other intestinal pathogens, C. jejuni does not harbor pathogen-defining toxins that explicitly contribute to disease in humans. This makes understanding Campylobacter pathogenesis challenging and supports a broad examination of bacterial factors that contribute to C. jejuni infection. Here we use a controlled human infection model to characterize C. jejuni transcriptional and genetic adaptations in vivo, along with a non-human primate infection model to validate our approach. We found variation in 11 genes is associated with either acute or persistent human infections and include products involved in host cell invasion, bile sensing, and flagella modification, plus additional potential therapeutic targets. Particularly, a functional version of the cell invasion protein A (cipA) gene product is strongly associated with persistently infecting bacteria and we went on to identify its biochemical role in flagella modification. These data characterize the adaptive C. jejuni response to primate infections and suggest therapy design should consider the intrinsic differences between acute and persistently infecting bacteria. Additionally, RNA-sequencing revealed conserved responses during natural host commensalism and human infections. 39 genes were differentially regulated in vivo across hosts, lifestyles, and C. jejuni strains. This conserved in vivo response highlights important C. jejuni survival mechanisms such as iron acquisition and evasion of the host mucosal immune response. These advances highlight pathogen adaptability across host species and demonstrate the utility of multidisciplinary collaborations in future clinical trials to study pathogens in vivo.

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Section: Campylobacter Gene Expression In Human Infection Samplesmentioning

confidence: 98%

Campylobacter jejuni transcriptional and genetic adaptation during human infection

et al. 2018

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“…In addition to Fur regulation, other regulatory proteins have been found that bind to the same promoters as Fur, indicating co-regulation of some cellular systems. In C. jejuni , a PAS-domain containing regulatory protein, termed HeuR, was found to positively regulate the heme utilization system and also bind to a promoter fragment that contains putative Fur binding sites (Ridley et al, 2006; Johnson et al, 2016). This regulator which is specific to the Campylobacter genus, did not impact transcription of Fur, indicating that it may work with Fur to control heme utilization in C. jejuni .…”

Section: Introductionmentioning

confidence: 99%

Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens

Richard

Kelley

Johnson

2019

Front. Cell. Infect. Microbiol.

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Iron is a transition metal utilized by nearly all forms of life for essential cellular processes, such as DNA synthesis and cellular respiration. During infection by bacterial pathogens, the host utilizes various strategies to sequester iron in a process termed, nutritional immunity. To circumvent these defenses, Gram-negative pathogens have evolved numerous mechanisms to obtain iron from heme. In this review we outline the systems that exist in several Gram-negative pathogens that are associated with heme transport and utilization, beginning with hemolysis and concluding with heme degradation. In addition, Gram-negative pathogens must also closely regulate the intracellular concentrations of iron and heme, since high levels of iron can lead to the generation of toxic reactive oxygen species. As such, we also provide several examples of regulatory pathways that control heme utilization, showing that co-regulation with other cellular processes is complex and often not completely understood.

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“…These data sets suggest Cj RidA could play a direct or indirect role in virulence, antibiotic resistance, acid adaptation, growth with bile salts, and hydrogen peroxide and oxygen stress. Finally, cj ridA is a member of the HeuR ( He me u tilization r egulator) regulon (Reuter et al, 2015; Johnson et al, 2016). HeuR is a PAS-domain containing regulator, and thought to be regulated in response to changing environmental cues (Reuter et al, 2015; Johnson et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cj1388 Is a RidA Homolog and Is Required for Flagella Biosynthesis and/or Function in Campylobacter jejuni

et al. 2019

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Campylobacter jejuni is the leading bacterial cause of acute gastroenteritis worldwide and thus significant to public health. C. jejuni primarily lives in the gastrointestinal tracts of poultry and can contaminate meat during processing. Despite a small genome, the metabolic plasticity of C. jejuni allows proliferation in chicken ceca and mammalian host intestines, and survival in environments with a variety of temperatures, pH, osmotic conditions, and nutrient availabilities. The exact mechanism of C. jejuni infection is unknown, however, virulence requires motility. Our data suggest the C. jejuni RidA homolog, Cj1388, plays a role in flagellar biosynthesis, regulation, structure, and/or function and, as such is expected to influence virulence of the organism. Mutants lacking cj1388 have defects in motility, autoagglutination, and phage infectivity under the conditions tested. Comparison to the RidA paradigm from Salmonella enterica indicates the phenotypes of the C. jejuni cj1388 mutant are likely due to the inhibition of one or more pyridoxal 5′-phosphate-dependent enzymes by the reactive enamine 2-aminoacrylate.

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The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni

Cited by 19 publications

References 41 publications

Campylobacter jejuni transcriptional and genetic adaptation during human infection

Campylobacter jejuni transcriptional and genetic adaptation during human infection

Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens

Cj1388 Is a RidA Homolog and Is Required for Flagella Biosynthesis and/or Function in Campylobacter jejuni

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