The genus Vibrio comprises an important group of ubiquitous bacteria of marine systems with a high infectious capacity for humans and fish, which can lead to death or cause economic losses in aquaculture. However, little is known about the evolutionary process that led to the adaptation and colonization of humans and also about the consequences of the uncontrollable use of antibiotics in aquaculture. Here, comparative genomics analysis and functional gene annotation showed that the species more related to humans presented a significantly higher amount of proteins associated with colonization processes, such as transcriptional factors, signal transduction mechanisms, and iron uptake. In comparison, those aquaculture-associated species possess a much higher amount of resistance-associated genes, as with those of the tetracycline class. Finally, through subtractive genomics, we propose seven new drug targets such as: UMP Kinase, required to catalyze the phosphorylation of UMP into UDP, essential for the survival of bacteria of this genus; and, new natural molecules, which have demonstrated high affinity for the active sites of these targets. These data also suggest that the species most adaptable to fish and humans have a distinct natural evolution and probably undergo changes due to anthropogenic action in aquaculture or indiscriminate/irregular use of antibiotics.

Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis, a Gram-negative bacterium described over a century ago. Despite broad vaccine coverage and treatment options, the disease is remerging as a public health problem especially in infants and older children. Recent data indicate re-emergence of the disease is related to bacterial resistance to immune defences and decreased vaccine effectiveness, which obviously suggests the need of new effective vaccines and drugs. In an attempt to contribute with solutions to this great challenge, bioinformatics tools were used to genetically comprehend the species of these bacteria and predict new vaccines and drug targets. In fact, approaches were used to analysis genomic plasticity, gene synteny and species similarities between the 20 genomes of Bordetella pertussis already available. Furthermore, it was conducted reverse vaccinology and docking analysis to identify proteins with potential to become vaccine and drug targets, respectively. The analyses showed the 20 genomes belongs to a homogeneous group that has preserved most of the genes over time. Besides that, were found genomics islands and good proteins to be candidates for vaccine and drugs. Taken together, these results suggests new possibilities that may be useful to develop new vaccines and drugs that will help the prevention and treatment strategies of pertussis disease caused by these Bordetella strains. Communicated by Ramaswamy H. Sarma

The Gram-negative bacillus Serratia marcescens, a member of Enterobacteriaceae family, is an opportunistic nosocomial pathogen commonly found in hospital outbreaks that can cause infections in the urinary tract, bloodstream, central nervous system and pneumonia. Because S. marcescens strains are resistant to several antibiotics, it is critical the need for effective treatments, including new drugs and vaccines. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 59 strains of S. marcescens. We found 759 core non-host homologous proteins, of which 87 are putative surface-exposed proteins, 183 secreted proteins, and 80 membrane proteins. From these proteins, we predicted seven candidates vaccine targets: a sn-glycerol-3-phosphate-binding periplasmic protein UgpB, a vitamin B12 TonB-dependent receptor, a ferrichrome porin FhuA, a divisome-associated lipoprotein YraP, a membrane-bound lytic murein transglycosylase A, a peptidoglycan lytic exotransglycosylase, and a DUF481 domain-containing protein. We also predicted two drug targets: a N(4)-acetylcytidine amidohydrolase, and a DUF1428 family protein. Using the molecular docking approach for each drug target, we identified and selected ZINC04259491 and ZINC04235390 molecules as the most favorable interactions with the target active site residues. Our findings may contribute to the development of vaccines and new drug targets against S. marcescens. Communicated by Ramaswamy H. Sarma

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine’s efficacy in in vivo models.

Histoplasma capsulatum is a thermodymorphic fungus that causes histoplasmosis, a systemic mycosis that presents different clinical manifestations, ranging from self-limiting to acute lung infection, chronic lung infection and disseminated infection. Usually, it affects severely immunocompromised patients although immunocompetent patients can also be infected. Currently, there are no vaccines to prevent histoplasmosis and the available antifungal treatment presents moderate to high toxicity. Additionally, there are few options of antifungal drugs. Thus, the aim of this study was to predict possible protein targets for the construction of potential vaccine candidates and predict potential drug targets against H. capsulatum. Whole genome sequences from four previously published H. capsulatum strains were analyzed and submitted to different bioinformatic approaches such as reverse vaccinology and subtractive genomics. A total of four proteins were characterized as good protein candidates (vaccine antigens) for vaccine development, three of which are membrane-bound and one is secreted. In addition, it was possible to predict four cytoplasmic proteins which were classified as good protein candidates and, through molecular docking performed for each identified target, we found four natural compounds that showed favorable interactions with our target proteins. Our study can help in the development of potential vaccines and new drugs that can change the current scenario of the treatment and prevention of histoplasmosis.

Ticks have coevolved with their hosts over millions of years, developing the ability to evade hemostatic, inflammatory, and immunological responses. Salivary molecules from these vectors bind to cytokines, chemokines, antibodies, complement system proteins, vasodilators, and molecules involved in coagulation and platelet aggregation, among others, inhibiting or blocking their activities. Initially studied to understand the complexities of tick–host interactions, these molecules have been more recently recognized for their potential clinical applications. Their ability to bind to soluble molecules and modulate important physiological systems, such as immunity, hemostasis, and coagulation, positions them as promising candidates for future therapeutic development. This review aims to identify the binding molecules present in tick saliva, determine their primary targets, and explore the tick species involved in these processes. By associating the binding molecules, the molecules to which they bind, and the effect caused, the review provides a basis for understanding how these molecules can contribute to possible future advances in clinical applications.