Avian reovirus (ARV) infections, characterized by severe arthritis, tenosynovitis, pericarditis, and poor weight gain, have become increasingly serious in recent years. The economic impact is significant as it causes growth inhibition and immunosuppression. Some commercial poultry in China have been widely vaccinated with available ARV vaccines; however, infections continue to occur even after vaccination. This study aimed to isolate a novel variant, ARV-SD19/11103, from the joint tissues of infected broiler chickens vaccinated with ARV vaccines in Shandong Province. Genetic evolution analysis of the major protective antigen σC gene in ARVs showed that ARV-SD19/11103 was located in the genotype cluster I but not in the same sub-cluster as the S1133 vaccine strain. The amino acid sequence similarity between SD19/11103 and vaccine strains S1133, 1733, and 2408 was <80%. After analyzing the amino acid sequences of the σC protein, 33 amino acid differences were found between the new variant isolate and the vaccine strains. This novel variant showed obvious pathogenicity in specific pathogen-free chicken embryos and chicks and could cause serious disease in chickens vaccinated with commercially available ARV vaccines. Cross-neutralization experiments further demonstrated a significant antigenic difference between the novel variant and genotype cluster I ARV strains. The novel variant strain isolated in this study provides an important theoretical basis for understanding the prevalence and genetic evolutionary characteristics of ARV variant strains in our country. This study identified the causes of ARVs circulating and emphasizes the needs for developing new vaccines against novel ARV variants.

Mycobacterium smegmatis (M.sm) is frequently used as an alternative model organism in Mycobacterium tuberculosis (M.tb) studies. While containing high sequence homology with M.tb, it is considered non-pathogenic in humans. As such it has been used to study M.tb and other infections in vivo and more recently been explored for potential therapeutic applications. A body of previous research has highlighted the potential of using genetically modified M.sm displaying rapid growth and unique immunostimulatory characteristics as an effective vaccine vector. Novel systems biology techniques can further serve to optimize these delivery constructs. In this article, we review recent advancements in vaccinomics tools that support the efficacy of a M.sm-based vaccine vector. Moreover, the integration of systems biology and molecular omics techniques in these pioneering studies heralds a potential accelerated pipeline for the development of next-generation recombinant vaccines against rapidly developing diseases.

In this study, we describe the combined effects of bedaquiline (BDQ) and the natural product curcumin (CUR) on Mycobacterium abscessus . In both in vitro and in vivo experiments, CUR enhanced BDQ’s inhibitory effect. This combination reduced M. abscessus survival under nutrient-deprived, hypoxic, and acidic conditions, accelerated ATP depletion, mitigated BDQ-induced respiratory compensation, and effectively improved infection outcomes in both normal and immunosuppressed mice. Metabolomics analysis revealed that adding CUR to BDQ exacerbated BDQ-dependent downregulation of purine and pyrimidine metabolism and amino acid synthesis. Thus, BDQ-CUR combination therapy could potentially be applied to treat M. abscessus infections. IMPORTANCE: Mycobacterium abscessus is an emerging pathogen that causes pulmonary infections, particularly in immunocompromised patients. It exhibits natural resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and physicians, thereby raising the need for innovative drug discovery. Here, we describe the combined effects of bedaquiline (BDQ) and curcumin (CUR) on M. abscessus . In vitro and in vivo studies have shown that CUR enhances the inhibitory effect of BDQ. Additionally, we investigated the synergistic effects at the metabolic level. Thus, these findings highlight the potential of BDQ-CUR combination therapy against M. abscessus infections.

Mycobacterium abscessus and Mycobacterium marinum are nontuberculous mycobacteria that pose significant challenges due to their high drug resistance and persistence in hostile host environments. Aminoacyl-tRNA synthetases, such as isoleucyl-tRNA synthetase (IleRS), are crucial for protein synthesis and represent promising targets for antimicrobial development. This study investigates the role of IleRS in mycobacterial growth, metabolism, and pathogenesis using conditional gene silencing combined with microbiological, metabolomic, and transcriptomic analyses. Our findings indicate that IleRS is essential for mycobacterial growth and survival during infection. Depletion of IleRS disrupts branched-chain amino acid and pantothenate biosynthesis, leading to metabolic vulnerabilities and impaired persistence in macrophages and in mouse infection models. Based on our metabolic findings, we tested drug susceptibility and found that depletion of IleRS enhances sensitivity to pyrazinamide, highlighting a synergistic effect that could improve tuberculosis treatment. Furthermore, global gene set enrichment analysis reveals that IleRS knockdown might promote bacterial clearance by upregulating cholesterol metabolism and lysosome organization processes in macrophages. These results establish IleRS as a potential therapeutic target, offering new insights into reducing drug resistance and enhancing current treatment regimens for mycobacterial infections, including tuberculosis.