3. Co-Infection of Mycoplasma hyopneumoniae with bacteria

Pasteurella multocida (PMULT), is a capsulated, Gram-negative coccobacillus, this primary pathogen can cause debilitating and fatal porcine pneumonia, especially resulting in pleuritic (Harper, Cox, Adler, & Boyce, 2011; Ross, 2006). Mhp and PMULT are associated with pneumonia at both the pig and herd levels, also the coincidental infections of Mhp and bacteria have also been studied for a long period (Fablet, Marois, et al., 2012). In cases with bacterial pneumonia, PMULT was the most prevalent infectious agent (Mores et al., 2015; Tocqueville, Kempf, Paboeuf, & Marois-Crehan, 2017), while the co-infection with Mhp and PMULT in gilts and sows can render the lungs more susceptible to PMULT colonization and infection(Ciprián, Pijoan, Cruz, Camacho, & Garza, 1988). Though pigs that have recovered from or vaccinated against Mhp infection were resistant to PMULT infection (Amass et al., 1994). In addition, Park and co-workers have elucidated the pathogenic mechanisms through which the Mhp increases the L-fucose composition to enhance adherence of PMULT type A to the bronchial and bronchiolar epithelial cells (C. Park et al., 2016). Moreover, Eileen et al reported that food which contain doxycycline was effective in fattening pigs to some extent and also controlling pneumonia which was due to PMULT and Mhp (Bousquet et al., 1998).
Actinobacillus pleuropneumoniae (APP) is a small, Gram-negative, encapsulated rod with typical coccobacillary morphology and an aetiological agent of porcine pleuropneumonia (Sassu et al., 2018). Concurrent infection with Mhp and APP is common, both of them are responsible for PRDC (Hege, Zimmermann, Scheidegger, & Stark, 2002). Mhp and APP are considered to be the most important primary bacterial respiratory pathogens associated with lung lesions (Fablet, Marois, et al., 2012), co-inoculation with Mhp and APP can induce more severe respiratory disorders in pigs (Haimi-Hakala et al., 2017). The detection rate of 0.1% for APP and 2.6% for Mhp were discovered in 3983 farms across Switzerland (Hege et al., 2002). Marois and colleagues indicated that concurrent infection with Mhp and APP had more severe lesions compared to single does infection in experimental pigs, pigs which were infected with the APP still remained healthy and lung lesions were only observed after the co-infection with Mhp(Marois et al., 2009). Meanwhile, the phagocytic abilities of alveolar macrophage had decreased in pigs co-infected with Mhp and APP (Caruso & Ross, 1990).
Lawsonia intracellularis(LI) are Gram-negative, obligate intracellular bacteria that cause proliferative enteropathy (PE), an economically important disease for the pig industry(Obradovic & Wilson, 2019). Dual infections with LI and Mhp caused the epithelial thickening and post-absorptive metabolic functions altering in pigs that result in reduced nutrient absorption, reductions in growth performance and feed efficiency (Helm, Curry, Schwartz, Lonergan, & Gabler, 2019; Helm, Outhouse, Schwartz, Lonergan, et al., 2018). Helm et al confirmed that, a dual enteric and respiratory pathogen challenge reduced average daily weight gain (ADG), average daily feed intake (ADFI), Gain:Feed (G:F) and tissue accretion in growing pigs(Helm, Outhouse, Schwartz, Dekkers, et al., 2018).
Moreover, studies have shown that immunosuppression caused by the predisposing of Mhp infection, can downregulate the phagocytic response , causing more serious clinical symptoms through the exposition to other bacterial pathogens, such as Bordetella bronchiseptica ,Haemophilus parasuis , Trueperella pyogenes and streptococci or staphylococci in field outbreaks of MPS(Caruso & Ross, 1990; Maes et al., 2018). It was also, reported that concurrent infections with different Mhp strains have been detected in the same field (Vranckx et al., 2011; Vranckx, Maes, Sacristan Rdel, Pasmans, & Haesebrouck, 2012), resulting in higher severity and prevalence of Mycoplasma-like lung lesions in slaughter pigs (Michiels, Vranckx, et al., 2017). Annelies and colleagues also demonstrated that, pigs that were co-infected with highly virulent strain F7.2C and the low virulent strain F1.12A, showed more severity lung lesions, coughed and larger log copies of Mhp in the bronchoalveolar lavag (Michiels, Arsenakis, et al., 2017). However, simultaneous infection with M. hyorhinis and Mhp did not aggravate the observed lung lesions (Luehrs et al., 2017), the results indicated that different virulent strain can interact with each other, but not between different species of mycoplasma. Further studies is needed to focus on the exact mechanism of how these bacterial pathogens interact with Mhp.