Wei SH, et al. Clin Exp Vaccine Res. 2015 Jul;4(2):121-129. https://doi.org/10.7774/cevr.2015.4.2.121

Salmonella enterica serovar Typhimurium, a non-typhoidal food-borne pathogen, causes acute enterocolitis, bacteremia, extraintestinal focal infections in humans. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) contribute to invading into host cellular cytosol, residing in Salmonella-containing vacuoles for intracellular survival, and inducing cellular apoptosis. This study aimed to better understand the mechanism underlying apoptosis in Salmonella-infected macrophages. S. Typhimurium SL1344 was used to evaluate extrinsic and intrinsic apoptosis pathways in THP-1 monocyte-derived macrophages in response to Salmonella infection. Activated caspase-3-induced apoptosis pathways, including extrinsic (caspase-8-mediated) and intrinsic (caspase-9-mediated) pathways, in Salmonella-infected macrophages were verified. THP-1 cells with dysfunction of TLR-4 and TLR-5 and Salmonella SPI-1 and SPI-2 mutants were constructed to identify the roles of the genes associated with programmed cell death in the macrophages. Caspase-3 activation in THP-1 macrophages was induced by Salmonella through TLR-4 and TLR-5 signaling pathways. We also identified that SPI-1 structure protein PrgH and effectors SipB and SipD, but not SPI-2 structure protein SsaV, could induce apoptosis via caspase-3 activation and reduce the secretion of inflammation marker TNF-α in the Salmonella-infected cells. The two effectors also reduced the translocation of the p65 subunit of NF-κB into the nucleus and the expression of TNF-α, and then inflammation was diminished. Non-typhoid Salmonella induced apoptosis of macrophages and thereby reduced inflammatory cytokine production through the expression of SPI-1. This mechanism in host-pathogen interaction may explain why Salmonella usually manifests as occult bacteremia with less systemic inflammatory response syndrome in the bloodstream infection of children.

The epidemiology of nontyphoidal Salmonella (NTS) resistant to ciprofloxacin or ceftriaxone and its impact on patients' clinical course are rarely reported. Children with culture-proven salmonellosis treated in a medical center in northern Taiwan in 2017 were enrolled. To trace the source of Salmonella, Salmonella isolated from food samples were collected from markets. Antimicrobial susceptibility and serotypes were determined. Among the 453 isolates, 122 (26.9%) were highly antimicrobial-resistant, as defined by resistance to ciprofloxacin or ceftriaxone or both. The most prevalent highly resistant serotype was S. Anatum (66, 54.1%). Salmonella was detected in 94.1%, 66.7%, and 8.6% of examined pork, chicken, and vegetables examined, respectively. S. Anatum (6, 21.4%) and S. Derby (6, 21.4%) were the major serotypes isolated. Majority of the S. Anatum (5, 83.3%) were highly antimicrobial-resistant. More patients infected by highly resistant Salmonella required carbapenem treatment (OR = 23.5, 95% confidence interval [CI] 2.8-192.7, P < 0.001). Patients with ceftriaxone-resistant NTS infections had a significantly longer hospital stay than others (P < 0.001). Totally, 34 (7.5%) presented with invasive diseases (31 bacteremia, 1 intestinal perforation, 1 toxic megacolon and 1 septic arthritis). Risk factors for invasive disease included prolonged fever for ≧5 days and infection occurring in warmer season from May to October. The rise of ambient temperature in northern Taiwan was associated with increasing Salmonella infections. Retail meats were the main source of highly antimicrobial-resistant NTS in northern Taiwan. Highly antimicrobial resistance significantly impacted the clinical course and treatment of children with NTS infection.

Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.

Background: The aim of this study was to identify risk factors for Clostridium difficile infection (CDI) and its attributable mortality and to propose methods to prevent CDI and improve patients' outcomes. Methods: CDI was defined as diarrheal patients with stool samples that were positive for C. difficile toxin. Clinical presentations of all patients with CDI and two times as many age- and sex-matched culture-negative controls at the Chang Gung Memorial Hospital in 2014 were identified and compared by multivariate, nonparametric, and Kaplan-Meier survival analysis. Results: There were no significant differences in ages, sex, or Charlson comorbidity indexes between the CDI group (n = 42) and the control group (n = 86). The multivariate analysis indicated that underlying peptic ulcer disease and previous use of gastric acid inhibitors or third-generation cephalosporins for at least 3 days were significantly more common in patients with CDI than in the controls. Charlson scores were associated with mortality due to CDI. Recommended treatment using oral vancomycin to treat patients with Charlson score >= 5 and oral metronidazole or vancomycin to treat those with moderate underlying disease (Charlson score >= 2 and <= 5) significantly increased survival in these patients (p = 0.001). Conclusions: Oral vancomycin given to patients with high Charlson scores and oral metronidazole or vancomycin to patients with moderate Charlson scores decreased mortality due to CDI. Restricting the use of third-generation cephalosporins and gastric acid inhibitors is recommended to prevent CDI in hospitalized patients.

Acinetobacter baumannii is an important nosocomial pathogen. To better understand the role of CsuA/BABCDE pilus of A. baumannii in virulence, bacterial biofilm formation, adherence and carbohydrate-mediated inhibition were conducted. CsuA/BABCDE pilus-producing (abbreviated Csu pilus) operon of A. baumannii ATCC17978 was cloned for analysis of biofilm formation on an abiotic plastic plate, bacterial adherence to respiratory epithelial human A549 cells and carbohydrate-mediated inhibition. The carbohydrates used for inhibition of biofilm formation and adherence to A549 cells included monosaccharides, pyranosides, and mannose-polymers. The Csu pilus of A. baumannii ATCC17978 was cloned and expressed into a non-pilus-producing Escherichia coli JM109, and was knocked out as well. The recombinant Csu (rCsu) pilus on E. coli JM109/rCsu pilus-producing clone observed by both electro-microscopy and atomic force microscopy showed abundant, while Csu-knockout A. baumannii ATCC17978 mutant appeared less or no pilus production. The E. coli JM109/rCsu pilus-producing clone significantly increased biofilm formation and adherence to A549 cells; however, the Csu-knockout mutant dramatically lost biofilm-making ability but, in contrast, increased adherence. Moreover, both of biofilm formation and adherence could be significantly inhibited by d-mannose and methyl-α-d-mannopyranoside in Csu pilus-producing E. coli JM109, whereas in A. baumannii ATCC17978, high concentration of carbohydrates was required for the inhibition, suggesting that Csu pilus is sensitive to d-mannose. This is the first study confirming that Csu pilus of A. baumannii belongs to mannose-sensitive type 1 pilus family and contributes to biofilm formation and bacterial adherence to human epithelial cells.