Pham, H. T. T. | bioRxiv Science

bioRxiv2025

Prevalence of Campylobacter and non-typhoidal Salmonella along broiler chicken production and distribution networks, Vietnam

Campylobacter and non-typhoidal Salmonella (NTS) are among the most common foodborne pathogens found in chickens at any production stage and cause gastroenteritis in humans. This study aimed to estimate the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in broiler production and distribution networks (PDN) using a Bayesian approach. A cross-sectional study was conducted in four provinces in northern Vietnam between March 2021 and March 2022. A total of 102 sites, including live bird markets, slaughter facilities (slaughterhouses and slaughter points), and their supplying farms, were randomly selected for sampling. Cecal and environmental samples were cultured for isolation of Campylobacter and NTS, with serotypes of NTS determined by targeted analysis of whole genome sequences. Bayesian models were developed to estimate the prevalence of Campylobacter at two levels (bird-level and site-level) and NTS at site-level. The selected best-fitted models indicated that C. jejuni prevalence was primarily influenced by site type, while C. coli was affected by both province and site types. For NTS, only site type was included. The highest overall prevalence of infected broilers was estimated on farms for C. coli (26.2% [95% High Density Interval (HDI): 19.0-36.0%]) and C. jejuni (19.9% [95%HDI 13.0-27.0%]). Slaughter points (97.6% [95%HDI 63.3-99.9%]) and wholesale markets (91.7% [95%HDI 28.2-99.9%]) had the highest probability of C. coli and C. jejuni contamination, respectively, but retail markets had the highest proportion of infected broilers at contaminated sites. NTS contamination was more frequent in markets and slaughter facilities (42.8% [95%HDI 30.8-57.1%]) than on farms (18.6% [95%HDI 9.5-30.1%]). Among 16 detected NTS serotypes, S. Infantis and S. Kentucky were the most common. These findings highlight the widespread contamination of broiler PDNs with Campylobacter and NTS in northern Vietnam, emphasizing the need for enhanced surveillance and control measures in PDNs to mitigate the risk of foodborne transmission. Author SummaryCampylobacter spp. and non-typhoidal Salmonella (NTS) are enteric pathogens that are key global pathogens causing diarrheal diseases. The Campylobacter species that are most frequently responsible for human diseases (campylobacteriosis) are Campylobacter jejuni (C. jejuni) and Campylobacter coli (C. coli). The severity of the salmonellosis depends on host factors and the serotype of NTS. Poultry and poultry products are recognized as major sources of NTS and Campylobacter infections in humans. In Vietnam, these pathogens have been detected in the broiler production and distribution networks (PDN). Factors that may increase the risk of transmission of those pathogens include low biosecurity practices, inadequate waste management, and high farm density. In this work, we estimated the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in PDN markets and slaughterhouses and farms supplying these facilities in four provinces in northern Vietnam. We estimated a high prevalence of Campylobacter contamination in slaughter points and wholesale markets and higher NTS contamination in slaughter facilities and markets than in farms. S. Infantis was one of the most frequently identified serovars. However, it was not reported as being frequently detected in humans in Vietnam. Therefore, serovar may vary depending on the source and region of contamination. Our results help us look at levels of infection/contamination with Campylobacter and NTS in the broiler PDNs, thus informing stakeholders to prevent and control campylobacteriosis and salmonellosis.

microbiology↗

bioRxiv2022

STAT5 Gain-of-Function Variants Promote Precursor T-Cell Receptor Activation to Drive T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T-cell cancer. Hotspot mutations in JAK-STAT pathway members IL7R, JAK1 and JAK3 were analyzed in depth. However, the role of STAT5A or STAT5B mutations promoting their hyperactivation is poorly understood in the context of T-cell cancer initiation and acute leukemia progression. Importantly, the driver mutation STAT5BN642H encodes the most frequent activating STAT5 variant in T-ALL associated with poor prognosis. Here, we show that hyperactive STAT5 promotes early T-cell progenitor (ETP)-ALL-like cancer in mice and upregulated genes involved in T-cell receptor signaling (TCR), even in absence of surface TCR promoting. Importantly, these genes were also overexpressed in human T-ALL and other STAT5-dependent T-cell cancers. Moreover, human T-ALL cells were sensitive to pharmacologic inhibition by dual STAT3/5 degraders or ZAP70 tyrosine kinase blockers. Thus, we define STAT5 target genes in T-ALL that promote pre-TCR signaling mimicry. We propose therapeutic targeting using selective ZAP70 or STAT3/5 inhibitors in a subgroup of T-ALL patients with prominent IL-7R-JAK1/3-STAT5 activity. SignificanceWe provide detailed functional characterizations of hyperactive STAT5A or STAT5B in thymic T-cell development and transformation. We found that hyperactive STAT5 transcribes T-cell-specific kinases or pre-TCR signaling hubs to promote T-ALL. Biomolecular and next-generation-sequencing methods, transgenesis and pharmacologic interference revealed that hyperactive STAT5 is a key oncogenic driver that can be targeted in T-ALL using STAT3/5 or SYK family member tyrosine kinase inhibitors. Conflict of interestThe authors declare no potential conflicts of interest.

cancer biology↗