Integrating AI into epitope prediction is transforming vaccine design by delivering unprecedented accuracy, speed, and efficiency. This review synthesizes recent breakthroughs particularly CNNs, transformers, and GNNs highlighting experimentally validated models like MUNIS and GraphBepi that reveal previously overlooked epitopes. By benchmarking AI tools against traditional methods, we identify structural data integration as pivotal, offering practical strategies to translate computational predictions into actionable experimental workflows for next-generation vaccines.

Pathogens are able to breach the intestinal barrier, and different bacterial species can display different abilities to colonize hosts and induce inflammation. Inflammatory response studies induced by enteropathogens as Escherichia coli are interesting since it has acquired diverse genetic mobile elements, leading to different E. coli pathotypes. Diarrheagenic E. coli secrete toxins, effectors and virulence factors that exploit the host cell functions to facilitate the bacterial colonization. Many bacterial proteins are delivered to the host cell for subverting the inflammatory response. Hereby, we have highlighted the specific processes used by E. coli pathotypes, by that subvert the inflammatory pathways. These mechanisms include an arrangement of pro- and anti-inflammatory responses to favor the appropriate environmental niche for the bacterial survival and growth.

Burkholderia pseudomallei is the causative agent of melioidosis, an endemic disease in tropical areas around the world. Cumulative human cases have demonstrated that melioidosis is prevalent and increasingly recognized in the American continent. Even though the first reports of melioidosis in Mexico, Central America, and the Caribbean Islands date back to the late 1940s, the potential of the disease as a public health concern in the region has not been fully appreciated. Unfortunately, recent studies predicting the global distribution of the disease and the demonstration of melioidosis endemicity in Puerto Rico have not increased recognition of the disease by health professionals in this region. Furthermore, a lack of both diagnostic capacity and awareness of the disease has resulted in a limited number of studies that have attempted to accurately determine its prevalence and geographical distribution. In this review, a summary of reported cases in the countries of this region are presented, as well as recommendations to increase the diagnosis and awareness of the disease as an important public health problem in Mexico, Central America, and the Caribbean islands.

Burkholderia pseudomallei (Bpm) is a Gram-negative bacterium and the causative agent of melioidosis. Despite advances in our understanding of the disease, Bpm poses a significant health risk, especially in endemic regions, where treatment requires prolonged antibiotic therapy. Even though the respiratory and percutaneous routes are well documented and considered the main ways to acquire the pathogen, the gastrointestinal tract is believed to be an underreported and underrecognized route of infection. In the present study, we describe the development of in vitro and in vivo models to study Bpm gastrointestinal infection. Further, we report that the Type 6 Secretion System (T6SS) and type 1 fimbriae are important virulence factors required for gastrointestinal infection. Using a human intestinal epithelial cell line and mouse primary intestinal epithelial cells (IECs), we demonstrated that Bpm adheres, invades, and forms multinucleated giant cells, ultimately leading to cell toxicity. We demonstrated that mannose-sensitive type 1 fimbria is involved in the initial adherence of Bpm to IECs, although the impact on full virulence was limited. Finally, we also showed that Bpm requires a functional T6SS for full virulence, bacterial dissemination, and for lethality in mice infected by the intragastric route. Overall, we showed that Bpm is an enteric pathogen, that type 1 fimbria is important for Bpm intestinal adherence and identify a new role for T6SS as a key virulence factor in gastrointestinal infection. These studies highlight the importance of gastrointestinal melioidosis as an understudied route of infection and open a new avenue for the pathogenesis of Bpm.

Melioidosis is a disease caused by the Gram-negative bacillus Burkholderia pseudomallei (Bpm), commonly found in soil and water of endemic areas. Naturally acquired human melioidosis infections can result from either exposure through percutaneous inoculation, inhalation, or ingestion of soil-contaminated food or water. Our prior studies recognized Bpm as an effective enteric pathogen, capable of establishing acute or chronic gastrointestinal infections following oral inoculation. However, the specific mechanisms and virulence factors involved in the pathogenesis of Bpm during intestinal infection are unknown. In our current study, we standardized an in vitro intestinal infection model using primary intestinal epithelial cells (IECs) and demonstrated that Bpm requires a functional T6SS for full virulence. Further, we performed dual RNA-seq analysis on Bpm-infected IECs to evaluate differentially expressed host and bacterial genes in the presence or absence of a T6SS. Our results showed a dysregulation in the TNF-α signaling via NF-κB pathway in the absence of the T6SS, with some of the genes involved in inflammatory processes and cell death also affected. Analysis of the bacterial transcriptome identified virulence factors and regulatory proteins playing a role during infection, with association to the T6SS. By using a Bpm transposon mutant library and isogenic mutants, we showed that deletion of the bicA gene, encoding a putative T3SS/T6SS regulator, ablated intracellular survival and plaque formation by Bpm and impacted survival and virulence when using murine models of acute and chronic gastrointestinal infection. Overall, these results highlight the importance of the type 6 secretion system in the gastrointestinal pathogenesis of Bpm.