Campylobacter: Animal Reservoirs, Human Infections, and Options for Control

Campylobacteriosis is a frequently diagnosed disease in humans. Most infections are considered foodborne and are caused by Campylobacter jejuni and C. coli. The animal reservoirs of these Campylobacter species, and the sources and routes of transmission, are described and discussed in this chapter. Most warm-blooded animals can be colonized by Campylobacter, but avian species, and in particular poultry, are preferred hosts. Much of the world’s poultry production is colonized by Campylobacter. Source attribution studies estimate that 20–40% of cases are attributed to the handling and consumption of chicken meat, while up to 80% of cases are due to Campylobacter found in the chicken reservoir. The difference suggests that routes other than through the food chain, i.e., environmental contamination, are important. The epidemiology of infections in humans differs between industrialized and low- and middle-income countries. Thus, the most effective interventions would be targeted to primary production. To date, only improved biosecurity is available. If effectively implemented, strict biosecurity can reduce the number of Campylobacter-positive flocks, but implementation to this level has proved difficult for the poultry industry. Available interventions in chicken processing plants can substantially reduce Campylobacter numbers on carcasses and consequently reduce the risk to humans. Public health strategies therefore utilize control programs, which aim at reducing the level of Campylobacter by measures along the food chain. It is now recognized that commercially acceptable complementary interventions for primary production, such as vaccines and feed additives, are urgently needed. Once Campylobacter in poultry is controlled then other minor sources of Campylobacter including contaminated drinking water, direct contact with (pet) animals, and other food items (e.g., red meat and milk) can be addressed

Genomic Characterization of Campylobacter jejuni Strain M1

Campylobacter jejuni strain M1 (laboratory designation 99/308) is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1

Identification of hyperinvasive Campylobacter jejuni strains isolated from poultry and human clinical sources

Campylobacter jejuni causes gastroenteritis with a variety of symptoms in humans. In the absence of a suitable animal model, in vitro models have been used to study virulence traits such as invasion and toxin production. In this study, 113 C. jejuni isolates from poultry and poultry-related (n=74) environments as well as isolates from human cases (n=39) of campylobacteriosis and bacteraemia were tested for invasiveness using INT 407 cells. The method was sufficiently reproducible to observe a spectrum of invasiveness amongst strains. As a result, strains were classified as low, high and hyper-invasive. The majority of strains (poultry and human) were low invaders (82 % and 88 %, respectively). High invasion was found for 5 % of human strains and 11 % of poultry-related isolates. However, only 1 % of poultry strains were classified as hyperinvasive compared to 13 % of human isolates (P=0.0182). Of those isolates derived from the blood of bacteraemic patients, 20 % were hyperinvasive, though this correlation was not statistically significant. An attempt was made to correlate invasiveness with the presence of seven genes previously reported to be associated with virulence. Most of these genes did not correlate with invasiveness, but gene cj0486 was weakly over-represented, and a negative correlation was observed for the gene ciaB. This trend was stronger when the two genes were analysed together, thus ciaB– cj0486+ was over-represented in high and hyperinvasive strains, with low invaders more commonly found to lack these genes (P=0.0064)

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

The ecology of Campylobacter jejuni in avian and human hosts and in the environment

AbstractCampylobacter jejuni, and its close relative C. coli, are highly successful bacteria colonizing the intestinal mucosa of a wide range of avian and animal hosts, including humans. In general, this colonization is either as a commensal, as in birds, or is an asymptomatic transient infection, as in livestock and in humans in endemic regions. However, in susceptible human populations, infection causes acute bacterial enteritis. The ecology of the organism for each outcome of colonization is considered, and evidence suggests that disease symptoms reflect the unfortunate consequences of the expression of bacterial factors associated with adaptation to the host gut environment. Susceptibility to disease appears to be associated with lack of acquired immunity. Although campylobacters do not grow outside the host, they can remain viable for long periods in water, foods, etc. Under such conditions, the organisms adapt to numerous hostile environmental stresses. Although such stressed organisms may be viable, the infectivity of surviving bacteria becomes severely compromised over time. Thus, the comparison of Campylobacter ecology in different environments suggests that increasing trends in human campylobacteriosis represent an unfortunate consequence of: decreasing human immunity because of reduced exposure to stress-compromised organisms; intensive farming practices creating monocultures of some strains; and improved processing and retail practices increasing the viability of campylobacters in food reaching the consumer