Changes in pathogenicity and immunogenicity of Mycoplasma mycoides subsp. mycoides strains revealed by comparative genomics analysis

Abstract

Mycoplasma mycoides subsp. mycoides is the causative agent of contagious bovine pleuropneumonia. A pathogenic strain BEN-1 was isolated from bovine lung and underwent continuous passages in rabbits for 468 generations. During this process, the strain’s strong virulence became weak and, gradually, it lost the ability to confer protective immunity in cattle but developed virulence in rabbits. In order to gain insight into the mechanisms behind the reduction in virulence and the loss of immunogenicity, we sequenced five representative strains of the BEN series, including the original strain (BEN-1), the strain generation that first acquired virulence in rabbits (BEN-50), the two vaccine strain generations (BEN-181 and BEN-326), and the strain generation showing the greatest loss of immunogenicity (BEN-468). The gene mutation rate in the four different propagation stages varied greatly, and over half of variations observed in each generation were removed during the propagation process. However, the variation maintained in the BEN-468 generation might contribute to its changes in virulence and immunogenicity. We thus identified 18 genes associated with host adaptation, six genes contributing to virulence in cattle, and 35 genes participating in conferring immunity in cattle. These findings might help us optimize the vaccine to obtain more effective immunization results.

Mmm-derived lipid-associated membrane proteins activate IL-1β production through the NF-κB pathway via TLR2, MyD88, and IRAK4

“…IL-1β regulation by the NF-κB signaling pathway plays an important role in shaping the inflammatory response against pathogens 8 . Previous reports indicated that after 2 μg/mL Mycoplasma bovis -derived LAMPs stimulation, the expression of IL-1β reached the peak at 12 h. In this study, we found that 1 μg/mL of Mmm-derived LAMPs could stimulate IL-1β expression to the peak levels at 6 h. Although the disease caused by Mmm and M. bovis exhibited similar clinical symptoms and pathological anatomy 4 , 6 – 8 , the expression kinetics of IL-1β in Mmm-derived LAMPs-stimulated EBL cells were different from M. bovis -derived LAMPs-stimulated EBL cells.…”

“…Mmm enters and colonizes respiratory epithelial cells of cattle when they inhale aerosols in contaminated air 4 , 16 . We previously determined that the P19 protein contributes to Mmm adherence to EBL cells 7 .…”

“…China, where CBPP was eradicated through the use of the Ben-181 vaccine, has been officially certified as a CBPP-free country by OIE. However, the disease still exists and spreads in many African contries 4 . Although many efforts have been taken to explore its pathogenesis, the molecular pathways of pathology and immune inflammatory responses associated with Mmm infection remains largely unknown 5 .…”

Dynamic Evolution Hypothesis of Organisms

“…To date, the adaptive tuning of mutation rates has been documented using laboratory evolution experiments of microorganisms adapting to new conditions (31,35,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). For instance, one long-term experimental evolution on Escherichia coli adapting to a new medium shows its mutation rate is increased by approximately 150-fold, and then reduced up to 60 % by increased adaptation (39).…”

“…Ecological studies show that increased investments into reproduction and lifespan may not always lead to increases of individual fitness, but their contributions to individual fitness will eventually decrease to virtually zero due to ecological constraints, leading to selection against further investments (23)(24)(25)(26). In particular, long-term studies on experimental evolution demonstrate that organismal evolution is subject to decreased fitness returns with increased adaptations in constant environments (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40); meanwhile, mutation rates also exhibit adaptive tuning with an initial increase and subsequent decrease as the putative adaptation peak is achieved (31,35,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). Moreover, one laboratory-based evolutionary study demonstrates a transition from selective evolution to neutral evolution with increased adaptation (34).…”