Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP.

In the current study, two Salmonella Typhimurium strains, JOL 912 and JOL 1800, were engineered from the wild-type JOL 401 strain through in-frame deletions of the lon and cpxR genes, with JOL 1800 also lacking rfaL. These deletions significantly attenuated the strains, impairing their intracellular survival and creating unique immunological profiles. This study investigates the response of these strains to various abiotic stress conditions commonly experienced in vivo, including temperature, acidity, osmotic, and oxidative stress. Notably, cold stress induced a non-significant trend towards increased invasion by Salmonella compared to other stressors. Despite the observed attenuation, no significant alterations in entry mechanisms (trigger vs. zipper) were noted between these strains, although variations were evident depending on the host cell type. Both strains effectively localized within the cytoplasm, demonstrating their ability to invade and interact with the intracellular environment. Immunologically, JOL 912 elicited a robust response, marked by substantial activation of nuclear factor kappa B (NF-kB), and chemokines, interleukin 8 (CXCL 8) and interleukin 10 (CXCL 10), comparable to the wild-type JOL 401 (over a fourfold increase compared to JOL 1800). In contrast, JOL 1800 exhibited a minimal immune response. Additionally, these attenuations influenced the expression of cyclins D1 and B1 and caspases 3 and 7, indicating cell cycle arrest at the G2/M phase and promotion of the G0/G1 to S phase transition, alongside apoptosis in infected cells. These findings provide valuable insights into the mechanisms governing the association, internalization, and survival of Salmonella mutants, enhancing our understanding of their regulatory effects on host cell physiology.

Salmonella enterica serovar Typhimurium (STm) causes gastroenteritis and can progress to reactive arthritis (ReA). STm forms biofilms in the gut that secrete the amyloid curli, which we previously demonstrated can trigger autoimmunity in mice. HLA-B27 is a genetic risk factor for ReA; activation of the unfolded protein response (UPR) due to HLA-B27 misfolding is thought to play a critical role in ReA pathogenesis. To determine whether curli exacerbates HLA-B27-induced UPR, bone marrow-derived macrophages (BMDMs) isolated from HLA-B27 transgenic (tg) mice were used. BMDMs treated with purified curli exhibited elevated UPR compared to C57BL/6, and curli-induced IL-6 was reduced by pre-treating macrophages with inhibitors of the IRE1α branch of the UPR. In BMDMs, intracellular curli colocalized with GRP78, a regulator of the UPR. In vivo, acute infection with wild-type STm increased UPR markers in the ceca of HLA-B27tg mice compared to C57BL/6. STm biofilms that contain curli were visible in the lumen of cecal tissue sections. Furthermore, curli was associated with macrophages in the lamina propria, colocalizing with GRP78. Together, these results suggest that UPR plays a role in the curli-induced inflammatory response, especially in the presence of HLA-B27, a possible mechanistic link between STm infection and genetic susceptibility to ReA.

BACKGROUND: Foodborne diseases (FBDs) represent a significant risk to public health, with nearly one in ten people falling ill every year globally. The large incidence of foodborne diseases in African low- and middle-income countries (LMIC) shows the immediate need for action, but there is still far to a robust and efficient outbreak detection system. The detection of outbreak heavily relies on clinical diagnosis, which are often delayed or ignored due to resource limitations and inadequate surveillance systems.
METHODS: In total, 68 samples of non-typhoidal Salmonella isolates from human, animal and environmental sources collected between November 2021 and January 2023 were analyzed using sequencing methods to infer phylogenetic relationships between the samples. A source attribution model using a machine-learning logit-boost that predicted the likely source of infection for 20 cases of human salmonellosis was also run and compared with the results of the cluster detection.
RESULTS: Three clusters of samples with close relation (SNP difference < 30) were identified as non-typhoidal Salmonella in Harar town and Kersa district, Ethiopia. These three clusters were comprised of isolates from different sources, including at least two human isolates. The isolates within each cluster showed identical serovar and sequence type (ST), with few exceptions in cluster 3. The close proximity of the samples suggested the occurrence of three potential outbreaks of non-typhoidal Salmonella in the region. The results of the source attribution model found that human cases of salmonellosis could primarily be attributed to bovine meat, which the results of the phylogenetic analysis corroborated.
CONCLUSIONS: The findings of this study suggested the occurrence of three possible outbreaks of non-typhoidal Salmonella in eastern Ethiopia, emphasizing the importance of targeted intervention of food safety protocols in LMICs. It also highlighted the potential of integrated surveillance for detecting outbreak and identifying the most probable source. Source attribution models in combination with other epidemiological methods is recommended as part of a more robust and integrated surveillance system for foodborne diseases.

UNASSIGNED: Nontyphoidal Salmonella infection is one of the most common foodborne illnesses, and its oncogenic potential has been documented in animal models. The primary goal of this study was to examine whether individuals who were exposed to enteric Salmonella infection are more likely to develop colorectal cancer (CRC) than the general population through the linkage of 2 statewide public health surveillance databases.
UNASSIGNED: We designed a 2-stage probabilistic linkage, starting with 17,587 records of enteric salmonellosis reported to Michigan Department of Health and Human Services between 1992 and 2020. These records did not include unique identifiers (such as Social Security number [SSN]). The initial linkage to LexisNexis address history was conducted to obtain information to calculate each person\'s time in Michigan as well as SSN for the second linkage. The linkage to the state cancer registry was performed to obtain the observed number of CRC cases, while the expected number of CRC cases was calculated according to corresponding state CRC incidence by age, sex, and calendar year.
UNASSIGNED: Ninety-three percent of the initially identified salmonellosis records were sent to LexisNexis linkage, which returned address history, death, and SSN for 97% of the records. Further linkage to the statewide cancer registry identified 98 incident CRC cases. Overall, the observed-to-expected (O/E) ratio was not different from unity (0.833; 95% CI, 0.627-1.003).
UNASSIGNED: While the new linkage strategy was found effective and should be applicable to other health conditions, we cannot rule out bias due to incomplete or underreporting of the infection in estimating the risk of CRC.

Self-powered photoelectrochemical (PEC) sensing is a novel sensing modality. The introduction of dual-mode sensing and photoelectrocatalysis in a self-powered system enables both detection and sterilization purposes. To this end, herein, a self-powered multifunctional platform for the photoelectrochemical-fluorescence (PEC-FL) detection and in-situ inactivation of Salmonella enteritidis (SE) was constructed. The platform utilized Bi4NbO8Cl/V2CTx/FTO as a photoanode and CuInS2/FTO as a photocathode and incubated quantum dot (QDs) signaling probes on the surface of the photocathode. During detection, the system drives the transfer of photogenerated electrons between the dual photoelectrodes through the Fermi energy level difference. The photoanode amplifies the photoelectric signal, while the photocathode is solely dedicated to the immune recognition process. QDs provide an additional fluorescence signal to the system. Under optimal experimental conditions, the multifunctional platform achieves detection limits of 3.2 and 5.3 CFU/mL in PEC and FL modes respectively, with a detection range of 2.91 × 102 to 2.91 × 108 CFU/mL. With the application of an external bias voltage, it further promotes electron transfer between the dual photoelectrodes, inhibits the recombination of photogenerated electrons and holes. It generates a significant amount of superoxide radicals (·O2-) in the cathodic region, resulting in strong sterilization efficiency (99%). The constructed self-powered multifunctional platform exhibits high sensitivity and sterilization efficiency, it provides a feasible and effective strategy to enhance the comprehensive capability of self-powered sensors.

Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal anti-inflammatory drugs (NSAIDs).

Salmonella enterica serovar Newport is a human pathogen underreported in most developing countries. It is known for causing gastroenteritis and extraintestinal infections. In this case report, we report the case of ceftriaxone-resistant Salmonella enterica serovar Newport from South India, causing acute gastroenteritis in a sixty-year-old female patient having a history of antimicrobial therapy and recent hospital admission. Serovar Newport, especially among antibiotic-exposed patients, poses a significant public health threat due to its ability to acquire multidrug resistance. This emphasizes the necessity for robust surveillance and monitoring of nontyphoidal Salmonella infections, particularly given the limited data on serovar Newport in India. Vigilance in clinical practice and public health initiatives is crucial to effectively address the emergence and spread of multidrug-resistant strains.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common foodborne enteric pathogen that infects humans or mammals and colonizes the intestinal tract primarily by invading the host following ingestion. Meanwhile, ClpV is a core secreted protein of the bacterial type VI secretion system (T6SS). Because elucidating ClpV\'s role in the pathogenesis of T6SS is pivotal for revealing the virulence mechanism of Salmonella, in our study, clpV gene deletion mutants were constructed using a λ-red-based recombination system, and the effect of clpV mutation on SL1344\'s pathogenicity was examined in terms of stress resistance, motility, cytokine secretion, gut microbiota, and a BALB/c mouse model. Among the results, ClpV affected SL1344\'s motility and was also involved in cell invasion, adhesion, and intracellular survival in the MDBK cell model but did not affect invasion or intracellular survival in the RAW264.7 cell model. Moreover, clpV gene deletion significantly reduced the transcription levels of GBP2b, IFNB1, IL-6, NLRP3, NOS2, and TNF-α proinflammatory factor levels but significantly increased transcription levels of IL-4 and IL-10 anti-inflammatory factors. Last, ClpV appeared to closely relate to the pathogenicity of S. Typhimurium in vivo, which can change the gut environment and cause dysbiosis of gut microbiota. Our findings elucidate the functions of ClpV in S. Typhimurium and illustrating interactions between T6SS and gut microbiota help to clarify the mechanisms of the pathogenesis of foodborne diseases.

BACKGROUND: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS).
METHODS: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS.
RESULTS: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10- 3].
CONCLUSIONS: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS.