Transcriptomic Analysis of the Campylobacter jejuni Response to T4-Like Phage NCTC 12673 Infection

Abstract

Campylobacter jejuni is a frequent foodborne pathogen of humans. As C. jejuni infections commonly arise from contaminated poultry, phage treatments have been proposed to reduce the C. jejuni load on farms to prevent human infections. While a prior report documented the transcriptome of C. jejuni phages during the carrier state life cycle, transcriptomic analysis of a lytic C. jejuni phage infection has not been reported. We used RNA-sequencing to profile the infection of C. jejuni NCTC 11168 by the lytic T4-like myovirus NCTC 12673. Interestingly, we found that the most highly upregulated host genes upon infection make up an uncharacterized operon (cj0423–cj0425), which includes genes with similarity to T4 superinfection exclusion and antitoxin genes. Other significantly upregulated genes include those involved in oxidative stress defense and the Campylobacter multidrug efflux pump (CmeABC). We found that phage infectivity is altered by mutagenesis of the oxidative stress defense genes catalase (katA), alkyl-hydroxyperoxidase (ahpC), and superoxide dismutase (sodB), and by mutagenesis of the efflux pump genes cmeA and cmeB. This suggests a role for these gene products in phage infection. Together, our results shed light on the phage-host dynamics of an important foodborne pathogen during lytic infection by a T4-like phage.

Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

“…Phage infection enhanced the transcript levels of three other oxidative stress response genes, including OG1RF_10348, OG1RF_10983, and OG1RF_11314 encoding superoxide dismutase (sodA), NADH peroxidase (npr), and catalase (katA), respectively (Table S2B). In Campylobacter jejuni, mutations in the LysR-regulated gene ahpC, as well as sodB and katA, resulted in reduced plaquing efficiency by the phage NCTC 12673 (27). We hypothesize that phage tolerance during hypersensitivity to oxidative stress could be detrimental to E. faecalis and targeting such pathways could be used to control E. faecalis colonization.…”

“…Additionally, the discovery of phage-modulated host pathways could reveal potential therapeutic targets. Our understanding of bacterial cellular responses during phage infection is limited to transcriptomic analyses in Gram-negative bacteria, whereas Gram-positive genera are understudied (26)(27)(28)(29)(30)(31). Therefore, to fill this gap and further define the molecular underpinnings of enterococcal-phage interactions, we have taken a global genomics approach to identify enterococcal factors critical for productive infection by the lytic phage VPE25 (32).…”

Phage-specific metabolic reprogramming of virocells

“…Transcript underexpression may lead to diminished or abolished protein function of these efflux transporters in both virocells. Such under-expression of transporters contrasts with C. jejuni virocells where a multidrug transporter was over-expressed during myovirus infection in this pathogen [58]. Future work is needed to experimentally evaluate the purpose of such phage-specific virocell responses to infection and their potential ties to pathogenesis.…”

Bacteriophage-Insensitive Mutants of Antimicrobial-Resistant Salmonella Enterica are Altered in their Tetracycline Resistance and Virulence in Caco-2 Intestinal Cells

“…For instance, significant (p < 0.05) downregulation of three antibiotic resistance genes were observed by global transcriptomic analysis of multi-drug-resistant Acinetobacter baumanii infected with phage ∂Abp1 [25]. The enhanced expression of efflux pumps in both phage-resistant Campylobacter jejeuni and P. aeruginosa has also been documented [29,30], leading to speculation that efflux pumps and other AMR proteins may have dual roles in phage resistance. As lytic phages are currently being considered for control of antimicrobial resistant bacteria, further work into understanding the influence of phage resistance on antibiotic resistance genes (and particularly, those of AMR Salmonella) is clearly warranted.…”