The introduction of infected animals is believed to be the primary source of infection for M. bovis-free herds. Clinical disease does not seem necessary for the maintenance and dissemination of M. bovis in the cattle population. Although most of the animals shed M. bovis for few months, some cattle can shed intermittently for months (Biddle et al., 2003) or even years (Bayoumi et al., 1988). 

The transmission of M. bovis is generally by aerosol, due to the fact that it is well adapted to colonization of mucosal surfaces. The upper respiratory tract (URT) is the primary site of M. bovis colonization after nasal exposure. The teat canal and the genital tract have also been described as a route of infection (Wrathall et al., 2007). In young calves, ingestion of infected milk is an important method of transmission for M. bovis. Once, M. bovis enters in the URT, it can reside there without causing any effect on healthy cattle. But stress caused by climatic changes, weaning, transport, overcrowding and/or relocation to feedlots can make animals more susceptible to infection or develop the disease, triggering an outbreak (Bayoumi et al., 1988). 

The incubation period has been described from 2 to 7 days for the respiratory form. Incubation and shedding periods may also be affected by co-infectants, stress and management, among other factors. Furthermore, in some cases the excretion may be intermittent, making it difficult to detect and therefore to determine the duration of the excretion period (Biddle et al., 2003).  

After M. bovis incubation, it can be isolated from multiple body sites during early infection: URT, mammary gland, conjunctiva, urogenital tract and bacteraemia. The URT mucosa and the mammary gland appear to be the most important sites of persistence and shedding of M. bovis. A lowering of immune responses together with contact with other bacterial and viral pathogens, results in the onset of BRD (Maunsell et al., 2011).   
 

M. bovis was first reported in the USA in 1961 from a bovine mastitis case and probably exported to Israel via cattle importation. From there, M. bovis arrived in Europe in the mid1970s. The international cattle trade and cattle products like semen have enabled its silent spread to all continents. In 2017, New Zealand became the last of the major cattle-rearing countries to be infected with M. bovis. Finland had also remained free until 2012 but became infected via imported cattle. The New Zealand government decided to apply eradication plans for M.bovis. Since the isolation up to 2020, more than 1800 farms were affected and around 160,000 cattle were slaughtered in New Zealand. Complete eradication looks feasible, but it will be a challenge (Dudek et al., 2020).  

In Europe, M. bovis is believed to be responsible for 25-33% of outbreaks of calf pneumonia (Nicholas et al., 2002).  In beef cattle, the prevalence of M. bovis in non-stressed calves is generally low (0-7%) in lungs, nasal swabs or by serology. On the contrary, prevalence is high for comingled, transported or calves in a feedlot, contributing substantially to mortality and morbidity in feedlot cattle (Maunsell et al., 2011, Caswell et al., 2007). 

Clinical signs of M. bovis can be confused with other pathogens, especially when these clinical signs are respiratory. Suspicion of M. bovis often gains importance when antimicrobial treatments fail, and the problem persists. The diagnosis of M. bovis is based on culture or molecular detection mainly from bronchiolar lavages, swabs (from different organs), joint fluid or milk (individually or bulk tank). Over recent years, ELISA- and PCR-based methods have gradually replaced culture as the method of choice for detecting M. bovis, and the application of a novel real-time (RT)-PCR method makes a valuable new contribution in the context (Sachse et al., 2010).  

The culture isolation confers the benefit of obtaining a bank of clinical isolates, which can be used to determine molecular characteristics and antimicrobial resistance analysis. But, as is well known, the culture of M. bovis has several disadvantages. It is time-consuming, laborious and it can have contaminations of other bacteria or the influence of antimicrobials previously administered. Consequently, molecular methods are recently used to detect M. bovis (Sachse et al., 2010), or simultaneous detection of M. bovis with other mycoplasma species (multiplex PCRs; Cornelissen et al., 2017). Recently, multi-pathogen panel PCR are also used to detect M. bovis with other pathogens (virus or bacteria) related to BRD (Kishimoto et al., 2017). 

Antibody ELISA tests for serological diagnosis are widely available and can be targeted on sentinel calf groups and bulk milk to provide evidence of herd status. Serology is therefore best applied in surveillance of the herd status.  

In order to prevent and control M. bovis, the introduction of new healthy animals into the herd is crucial. The conduction of an ELISA test before introduction to assess prior exposure, and molecular detection for current suspects would offer control to latent or new infections. Additionally, some management practices can be performed to control M. bovis: adequate ventilation, cleaning and disinfection of animal areas, milk feeding control, monitoring clinical signs regularly and isolation of treated or infected animals.  

If M. bovis infection appears in a herd, an adequate antimicrobial treatment can be used. But, as mentioned before, some field isolates described resistance against some antimicrobials usually used in farm conditions (Lysnyansky & Ayling, 2016). 

As recently described by Dudek et al., (2021), data on the present commercial vaccines in use show that they are scarcely effective, one of these described an efficacy of 1%. This low efficacy indicates that the development of an effective M. bovis vaccine is still a pending task. Research must be done in different areas, for example: obtaining a robust experimental challenge model and expanding the proteomic knowledge of the pathogen, in order to detect novel secreted proteins that can be used as a potent vaccine for effective control of M. bovis infections. But above all, as described by Dudek et al., (2021), the use of vaccination against M. bovis, must be accompanied by measures or vaccines against other respiratory pathogens such as BVD, Mannheimia and possibly others.   

The current situation of M. bovis presents a difficult scenario to fight against this pathogen. The large antibiotic resistance to antimicrobial drugs frequently used in the field, added to the lack of an optimal vaccine, suggest that much more research is needed to obtain good control tools. In addition, the intrinsic characteristics of M. bovis, showing differences in virulence among field strains, the difficulty of diagnosis and the ability to become chronic or induce latent infections, make it a difficult pathogen to control. Considering that it is one of the main agents involved in BRD, good facility management, surveillance and control of other related pathogens is essential to minimize the impact of M. bovis on farms until new tools are developed. 
 

Author: Carlos Montbrau, DVM PhD; Ester Taberner, DVM PhD; Ricard March.

^References: 

^{Aebi, M., van den Borne, B. H. P., Raemy, A., Steiner, A., Pilo, P., & Bodmer,M. (2015). Mycoplasma bovis infections in Swiss dairy cattle: A clinical investigation. Acta Veterinaria Scandinavica, 57, 10.}  

^{Askar H., Chen S., Hao H., Yan X., Ma L., Liu Y., Chu Y., (2021). Immune evasion of Mycoplasma bovis. Pathogens, 10, 297.} 

^{Bayoumi, F. A., Farver, T. B., Bushnell, B., & Oliveria, M. (1988). Enzootic mycoplasmal mastitis in a large dairy during an eight-year period. Journal of the American Veterinary Medical Association, 192, 905–909.} 

^{Biddle, M. K., Fox, L. K., & Hancock, D. D. (2003). Patterns of mycoplasma shedding in the milk of dairy cows with intramammary Mycoplasma infection. Journal of the American Veterinary Medical Association, 223, 1163–1166.}  

^{Brown, D. R., May, M., Bradbury, J. M., & Johansson, K.-E. (2015). Mollicutes. Bergey’s Manual of Systematics of Archaea and Bacteria. 1–8.} 

^{Castillo-Alcala, F., Bateman, K. G., Cai, H. Y., Schott, C. R., Parker, L., Clark, M. E., Caswell, J. L. (2012). Prevalence and genotype of Mycoplasma bovis in beef cattle after arrival at a feedlot. American Journal of Veterinary Research, 73, 1932–1943. https://doi.org/10.2460/ajvr.73.12.1932} 

^{Caswell, J. L., & Archambault, M. (2007). Mycoplasma bovis pneumonia in cattle. Animal Health Research Reviews, 2, 161–186. https://doi.org/10.1017/S1466252307001351} 

^{Cornelissen, J. B. W. J., de Bree, F. M., van der Wal, F. J., Kooi, E. A., Koene, M. G. J., Bossers, A.,  Wisselink, H. J. (2017). Mycoplasma detection by triplex real-time PCR in bronchoalveolar lavage fluid from bovine respiratory disease complex cases. BMC Veterinary Research, 13, 97. https://doi.org/10.1186/s12917-017-1023-6} 

^{Dudek K., Szacawa E., Nicholas R.A.J., (2021). Recent developments in vaccines for bovine mycoplasmoses caused by Mycoplasma bovis and Mycoplasma mycoides subsp. mycoides. Vaccines, 9, 549.} 

^{Dudek K., Nicholas R.A.J., Szacawa E., Bednarek D. (2020). Mycoplasma bovis infections – occurrence, diagnosis and control. Pathogens, 9, 640.} 

^{Gagea M.I., Bateman K.G., Shanahan R.A., van Dreumel T., McEwen B.J., Carman S., Archambault M., Caswell J.L., (2006). Naturraly ocurring Mycoplasma bovis – associated pneumonia and polyarthritis in feedlot beef calves. J Vet Diagn Invest 18, 29-40.} 

 ^{Houlihan, M. G., Veenstra, B., Christian, M. K., Nicholas, R., & Ayling, R. (2007). Mastitis and arthritis in two dairy herds caused by Mycoplasma bovis. Veterinary Record, 160, 126–127. https://doi.org/10.1136/vr.160.4.126} 

^{Justice-Allen, A., Trujillo, J., Corbett, R., Harding, R., Goodell, G., & Wilson, D. (2010). Survival and replication of Mycoplasma species in recycled bedding sand and association with mastitis on dairy farms in Utah. Journal of Dairy Science, 93, 192–202. https://doi.org/10.3168/jds.2009-2474} 

^{Kishimoto, M., Tsuchiaka, S., Rahpaya, S. S., Hasebe, A., Otsu, K., Sugimura, S., Kobayashi, S., Komatsu, N., Nagai, M., Omatsu, T., Naoi, Y., Sano, K., Okazaki-Terashima, S., Oba, M., Katayama, Y., Sato, R., Asai, T.,  Mizutani, T. (2017). Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex. Journal of Veterinary Medical Science, 79, 517–523. https://doi.org/10.1292/jvms.16-0489} 

^{Lysnyansky, I., & Ayling, R. D. (2016). Mycoplasma bovis: Mechanisms of resistance and trends in antimicrobial susceptibility. Frontiers in Microbiology, 27(7), 595.} 

^{Lysnyansky, I., Sachse, K., Rosenbusch, R., Levisohn, S., & Yogev, D. (1999). The vsp locus of Mycoplasma bovis: Gene organization and structural features. Journal of Bacteriology, 181, 5734–5741.} 

^{Maunsell F.P., Woolums A.R., Francoz D., Rosenbusch R.F., Step D.L., WIlson D.J., Janzen E.D., (2011). Mycoplasma bovis infections in cattle. J Vet Intern Med 25, 772-783.} 

^{Nicholas, R. A. J., Ayling, R. D., & Stipkovits, L. (2002). An experimental vaccine for calf pneumonia caused by Mycoplasma bovis. Vaccine, 20, 3569–3575. https://doi.org/10.1016/S0264-410X(02)00340-7} 

^{Nicholas, R. A. J., Ayling, R. D., & McAuliffe, L. (2008). Bovine respiratory disease. In R. Nicholas, R. Ayling & L. McAuliffe (Eds.), Mycoplasma diseases of ruminants (pp. 132–168), Oxfordshire: CABI Wallingford. https://doi.org/10.1079/9780851990125.0000} 

^{Nicholas, R. A. J., Fox, L. K., & Lysnyansky, I. (2016). Mycoplasma mastitis in cattle: To cull or not to cull. The Veterinary Journal, 216, 142–147. https://doi.org/10.1016/j.tvjl.2016.08.001} 

^{Radaelli, E., Luini, M., Loria, G. R., Nicholas, R. A. J., & Scanziani, E. (2008). Bacteriological, serological, pathological and immunohistochemical studies of Mycoplasma bovis respiratory infection in veal calves and adult cattle at slaughter. Research in Veterinary Science, 85, 282–290. https://doi.org/10.1016/j.rvsc.2007.11.012} 

^{Rosales, R. S., Puleio, R., Loria, G. R., Catania, S., & Nicholas, R. A. J. (2017). Mycoplasmas: Brain invaders? Research in Veterinary Science, 113, 56–61. https://doi.org/10.1016/j.rvsc.2017.09.006} 

^{Rosenbusch, R. F. (1994). Biology and taxonomy of the Mycoplasmas. In H. W. Whitford, R. F. Rosenbusch & L. H. Lauerman (Eds.), Mycoplasmosis in animals: Laboratory diagnosis (pp. 3–11). Ames, Iowa: Iowa State University Press.} 

^{Sachse K., Salam H.S.H., Diller R., Schubert E., Hoffmann B., Hotzel H. (2010). Use of a novel real-time PCR technique to monitor and quantitate Mycoplasma bovis in cattle herds with mastitis and respiratory disease. The Veterinary Journal 186, 299-303.} 

^{Timsit, E., Arcangioli, M. A., Bareille, N., Seegers, H., & Assi_e, S.(2012). Transmission dynamics of Mycoplasma bovis in newly received beef bulls at fattening operations. Journal of Veterinary Diagnostic Investigation, 24, 1172–1176. https://doi.org/10.1177/1040638712463211} 

^{Van der Merwe, J., Prysliak, T., & Perez-Casal, J. (2010). Invasion of bovine peripheral blood mononuclear cells and erythrocytes by Mycoplasma bovis. Infection and Immunity, 78, 4570–4578. https://doi.org/10.1128/IAI.00707-10} 

^{Wang, Y., Liu, S., Li, Y., Wang, Q., Shao, J., Chen, Y., & Xin, J. (2016). Mycoplasma bovis-derived lipid-associated membrane proteins activate IL-1b production through the NF-jB pathway via toll-like receptor2 and MyD88. Developmental and Comparative Immunology, 55,111–118.} 

^{Wilson, D. J., Skirpstunas, R. T., Trujillo, J. D., Cavender, K. B., Bagley, C. V., & Harding, R. L. (2007). Unusual history and initial clinical signs of Mycoplasma bovis mastitis and arthritis in first-lactation cows in a closed commercial dairy herd. Journal of the American Veterinary Medical Association, 230, 1519–1523. https://doi.org/10.2460/javma.230.10.1519} 

^{Wrathall, A. E., Ayling, R. D., & Simmons, H. (2007). Risks of transmitting mycoplasmas by semen and embryo transfer techniques in cattle, sheep, goats and pigs. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources, 2(36), 1–31.}