Search

Bacterial type IV secretion systems (T4SSs) can mediate conjugation. The T4SS from Neisseria gonorrhoeae possesses the unique ability to mediate DNA secretion into the extracellular environment. The N. gonorrhoeae T4SS can be grouped with F-type conjugative T4SSs based on homology. We tested 17 proteins important for DNA secretion by N. gonorrhoeae for protein interactions. The BACTH-TM bacterial two-hybrid system was successfully used to study periplasmic interactions. By determining if the same interactions were observed for F-plasmid T4SS proteins and when one interaction partner was replaced by the corresponding protein from the other T4SS we aimed to identify features associated with the unique function of the N. gonorrhoeae T4SS as well as generic features of F-type T4SSs. For both systems, we observed already described interactions shared by homologs from other T4SSs as well as new and described interactions between F-type T4SS specific proteins. Furthermore, we demonstrate, for the first-time, interactions between proteins with homology to the conserved T4SS outer membrane core proteins and F-type specific proteins and we confirmed two of them by co-purification. The F-type specific protein TraH(N) was found to localize to the outer membrane and the presence of significant amounts of TraH(N) in the outer membrane requires TraG(N).

Chronic Helicobacter pylori (Hp) infection is considered to be the single most important risk factor for the development of gastric adenocarcinoma in humans, which is a leading cause of cancer-related death worldwide. Nonetheless, Hp infection does not always progress to malignancy, and, gastric adenocarcinoma can occur in the absence of detectable Hp carriage, highlighting the complex and multifactorial nature of gastric cancer. Here we review known contributors to gastric malignancy, including Hp virulence factors, featuring the vacuolating cytotoxin (VacA), the cytotoxin-associated gene A (CagA), and other bacterial components that promote chemotaxis, colonization, and the establishment of chronic inflammation. In addition, we discuss host factors including sex, age, and genetic polymorphisms associated with host inflammation. Moreover, we consider environmental variables that influence cancer risk, such as nutritional status, socio-economic status, and smoking. In addition to these relatively well-studied contributors to gastric cancer risk, the resident gastric microflora in humans have more recently been proposed as an additional risk factor for disease progression in Hp-infected individuals. Molecular approaches for microbe identification have revealed differences in the gastric microbiota composition between cancer and non-cancerous patients, as well as infected and uninfected individuals. Although the reasons underlying differences in microbial community structures are not entirely understood, gastric atrophy and hypochlorhydria that accompany chronic Hp infection may be a critical driver of gastric dysbiosis that promote colonization of microbes that contribute to increased risk of malignancy. However, definitive evidence that the gastric microbiota influences the emergence of gastric cancer does not exist. In summary, while controversial and unresolved, the importance of the gastric microbiota as a risk factor for gastric malignancy is a vital area of current research.