Infection, Transmission, Pathogenesis and Vaccine Development against Mycoplasma gallisepticum.

Mycoplasma sp. comprises cell wall-less bacteria with reduced genome size and can infect mammals, reptiles, birds, and plants. Avian mycoplasmosis, particularly in chickens, is primarily caused by Mycoplasma gallisepticum (MG) and Mycoplasma synoviae. It causes infection and pathology mainly in the respiratory, reproductive, and musculoskeletal systems. MG is the most widely distributed pathogenic avian mycoplasma with a wide range of host susceptibility and virulence. MG is transmitted both by horizontal and vertical routes. MG infection induces innate, cellular, mucosal, and adaptive immune responses in the host. Macrophages aid in phagocytosis and clearance, and B and T cells play critical roles in the clearance and prevention of MG. The virulent factors of MG are adhesion proteins, lipoproteins, heat shock proteins, and antigenic variation proteins, all of which play pivotal roles in host cell entry and pathogenesis. Prevention of MG relies on farm and flock biosecurity, management strategies, early diagnosis, use of antimicrobials, and vaccination. This review summarizes the vital pathogenic mechanisms underlying MG infection and recapitulates the virulence factors of MG-host cell adhesion, antigenic variation, nutrient transport, and immune evasion. The review also highlights the limitations of current vaccines and the development of innovative future vaccines against MG.

In silico structural homology modeling and functional characterization of Mycoplasma gallisepticum variable lipoprotein hemagglutin proteins.

Mycoplasma gallisepticum variable lipoprotein hemagglutin (vlhA) proteins are crucial for immune evasion from the host cells, permitting the persistence and survival of the pathogen. However, the exact molecular mechanism behind the immune evasion function is still not clear. In silico physiochemical analysis, domain analysis, subcellular localization, and homology modeling studies have been carried out to predict the structural and functional properties of these proteins. The outcomes of this study provide significant preliminary data for understanding the immune evasion by vlhA proteins. In this study, we have reported the primary, secondary, and tertiary structural characteristics and subcellular localization, presence of the transmembrane helix and signal peptide, and functional characteristics of vlhA proteins from M. gallisepticum strain R low. The results show variation between the structural and functional components of the proteins, signifying the role and diverse molecular mechanisms in functioning of vlhA proteins in host immune evasion. Moreover the 3D structure predicted in this study will pave a way for understanding vlhA protein function and its interaction with other molecules to undergo immune evasion. This study forms the basis for future experimental studies improving our understanding in the molecular mechanisms used by vlhA proteins.

A Computational Reverse Vaccinology Approach for the Design and Development of Multi-Epitopic Vaccine Against Avian Pathogen Mycoplasma gallisepticum.

Avian mycoplasma is a bacterial disease causing chronic respiratory disease (CRD) in poultry industries with high economic losses. The eradication of this disease still remains as a challenge. A multi-epitope prophylactic vaccine aiming the antigenic proteins of Mycoplasma gallisepticum can be a capable candidate to eradicate this infection. The present study is focused to design a multi-epitope vaccine candidate consisting of cytotoxic T-cell (CTL), helper T-cell (HTL), and B-cell epitopes of antigenic proteins, using immunoinformatics strategies. The multi-epitopic vaccine was designed, and its tertiary model was predcited, which was further refined and validated by computational tools. After initial validation, molecular docking was performed between multi-epitope vaccine construct and chicken TLR-2 and 5 receptors, which predicted effective binding. The in silico results specify the structural stability, precise specificity, and immunogenic response of the designed multi-epitope vaccine, and it could be an appropriate vaccine candidate for the M. gallisepticum infection.

Multi-epitope-Based Vaccine Designed by Targeting Cytoadherence Proteins of Mycoplasma gallisepticum.

Mycoplasma gallisepticum causes chronic respiratory disease in chickens leading to large economic losses in the poultry industry, and the impacts remain to be a great challenge for a longer period. Among the other approaches, a vaccine targeting the adhesion proteins of M. gallisepticum would be a promising candidate in controlling the infection. Thus, the present study is aimed to design a multi-epitope vaccine candidate using cytoadhesion proteins of M. gallisepticum through an advanced immunoinformatics approach. As a result, the multi-epitope vaccine was constructed, which comprised potential T-cell and B-cell binding epitopes with appropriate adjuvants. The designed multi-epitope vaccine represented high antigenicity with viable physiochemical properties. The prospective three-dimensional structure of the epitope was predicted, refined, and validated. The molecular docking analysis of multi-epitope vaccine candidates with the chicken Toll-like receptor-5 predicted effective binding. Furthermore, codon optimization and in silico cloning ensured high expression. Thus, the present finding indicates that the engineered multi-epitope vaccine is structurally stable and can induce a strong immune response. Furthermore, the multi-epitope vaccine is suggested to be a suitable vaccine candidate for the M. gallisepticum infection due to its effective binding capacity and precise specificity.