Abubakar Siddique

The current study was designed to explore the biosynthetic potential of sevadicin in Bacillus pumilus species and its interaction with bacterial drug target molecules. The non-ribosomal peptide (NRP) cluster in B. pumilus SF-4 was preliminarily confirmed using PCR-based screening, and the bioactivity of strain SF-4 culture extract was assessed against a set of human pathogenic strains. The susceptibility assay showed that strain SF-4 extract had higher inhibitory concentrations (312–375 µg/mL) than ciprofloxacin. Genome mining of B. pumilus strains (n = 22) using AntiSMASH and BAGEL identified sevadicin coding biosynthetic gene cluster only in strain SF-4, constitutes of two core biosynthetic genes, three additional biosynthetic genes, two transport-related genes, and one regulatory gene. The molecular docking of sevadicin with various putative bacterial drug targets such as dihydropteroate, muramyl ligase E, topoisomerase, penicillin-binding protein, and in vitro safety analyses were conducted with detailed ADMET screening. The results showed that sevadicin makes hydrophobic interaction with MurE (PDB ID: 1E8C and 4C13) via hydrogen bonding, suggesting bacterial growth inhibition by disrupting the cell wall synthesis pathway and exhibiting a secure biosafety profile. The stability and compactness of sevadicin/MurE complexes were assessed via molecular dynamic simulation using RMSD, RMSF, and Rg. The simulation results revealed the binding stability of sevadicin/MurE complexes and indicated that the complexes can't be easily deformed. In conclusion, the current study explored the biosynthesis of sevadicin in B. pumilus for the first time and found that sevadicin inhibits bacterial growth by inhibiting cell wall synthesis via targeting the MurE enzyme and exhibits no toxicity.

Salmonella is a significant zoonotic foodborne pathogen, and the global spread of multidrug-resistant (MDR) strains poses substantial challenges, necessitating alternatives to antibiotics. Among these alternatives, vaccines protect the community against infectious diseases effectively. This review aims to summarize the efficacy of developed Salmonella vaccines evaluated in various animal hosts and highlight key transitions for future vaccine studies. A total of 3221 studies retrieved from Web of Science, Google Scholar, and PubMed/Medline databases between 1970 and 2023 were evaluated. One hundred twenty-seven qualified studies discussed the vaccine efficacy against typhoidal and nontyphoidal serovars, including live-attenuated vaccines, killed inactivated vaccines, outer membrane vesicles, outer membrane complexes, conjugate vaccines, subunit vaccines, and the reverse vaccinology approach in different animal hosts. The most efficacious vaccine antigen candidate found was recombinant heat shock protein (rHsp60) with an incomplete Freund’s adjuvant evaluated in a murine model. Overall, bacterial ghost vaccine candidates demonstrated the highest efficacy at 91.25% (95% CI = 83.69–96.67), followed by the reverse vaccinology approach at 83.46% (95% CI = 68.21–94.1) across animal hosts. More than 70% of vaccine studies showed significant production of immune responses, including humoral and cellular, against Salmonella infection. Collectively, the use of innovative methods rather than traditional approaches for the development of new effective vaccines is crucial and warrants in-depth studies.

Bacterial regional demonstration after global dissemination is an essential pathway for selecting distinct finesses. However, the evolution of the resistome during the transition to endemicity remains unaddressed. Using the most comprehensive whole-genome sequencing dataset of Salmonella enterica serovar Gallinarum ( S . Gallinarum) collected from 15 countries, including 45 newly recovered samples from two related local regions, we established the relationship among avian-specific pathogen genetic profiles and localization patterns. Initially, we revealed the international transmission and evolutionary history of S . Gallinarum to recent endemicity through phylogenetic analysis conducted using a spatiotemporal Bayesian framework. Our findings indicate that the independent acquisition of the resistome via the mobilome, primarily through plasmids and transposons shapes a unique antimicrobial resistance profile among different lineages. Notably, the mobilome-resistome combination among distinct lineages exhibits a geographical-specific manner, further supporting a localized endemic mobilome-driven process. Collectively, this study elucidates resistome adaptation in the endemic transition of an avian-specific pathogen, likely driven by the localized farming style, and provides valuable insights for targeted interventions.