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Bacterial pathogens have evolved to manipulate host cell death and survival pathways for their intracellular persistence. Understanding the ability of a bacterium to induce or inhibit cell death is essential for elucidating the disease pathogenesis and suggesting potential therapeutic options to manage the infection. In recent years, apoptosis inhibition by different bacteria has been suggested as a mechanism of survival by allowing the pathogen to replicate and disseminate in the host. Mycoplasma bovis has evolved mechanisms to invade and modulate apoptosis of bovine peripheral blood mononuclear cells (PBMC), red blood cells (RBCs), primary macrophages and monocytes. To date, these mechanisms are poorly understood. Using apoptosis assays such as Annexin V binding, caspases activity, reactive oxygen species production, DNA fragmentation and differential gene expression we set out to determine how M. bovis modulates macrophage survival. Using the BoMac cell line, we report a significant reduction in STS-induced apoptosis through caspase dependent manner. Besides activating the NF-kβ pathway and inhibiting caspases 3, 6 and 9, M. bovis strain Mb1 also inhibits production of reactive oxygen species and DNA fragmentation of the host cell. We also report a significant up-regulation of the anti-apoptotic genes Bcl-2 and Bcl-X L upon infection. Our results indicate that M. bovis strain Mb1 inhibits the intrinsic pathway of apoptosis and up-regulate survival genes in BoMac cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the last few years, several outbreaks of pneumonia, systemically disseminated infection, and high mortality associated with Mycoplasma bovis (M. bovis) in North American bison (Bison bison) have been reported in Alberta, Manitoba, Saskatchewan, Nebraska, New Mexico, Montana, North Dakota, and Kansas. M. bovis causes Chronic Pneumonia and Polyarthritis Syndrome (CPPS) in young, stressed calves in intensively-managed feedlots. M. bovis is not classified as a primary pathogen in cattle, but in bison it appears to be a primary causative agent with rapid progression of disease with fatal outcomes and an average 20% mature herd mortality. Thus, there is a possibility that M. bovis isolates from cattle and bison differ in their pathogenicity. Hence, we decided to compare selected cattle isolates to several bison isolates obtained from clinical cases. We show differences in modulation of PBMC proliferation, invasion of trachea and lung epithelial cells, along with modulation of apoptosis and survival in alveolar macrophages. We concluded that some bison isolates showed less inhibition of cattle and bison PBMC proliferation, were not able to suppress alveolar macrophage apoptosis as efficiently as cattle isolates, and were more or less invasive than the cattle isolate in various cells. These findings provide evidence about the differential properties of M. bovis isolated from the two species and has helped in the selection of bison isolates for genomic sequencing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Mycoplasma bovis is one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis. M. bovis enters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction between M. bovis and the bovine innate immune system is not well understood. We hypothesized that M. bovis invades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant to M. bovis-monocyte interactions in vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes with M. bovis delays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report that M. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest that M. bovis takes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.