Mycobacterium tuberculosis (Mtb) is the oldest pathogen of the mankind, responsible for the Tuberculosis (TB) disease in humans. TB infection is the leading cause of morbidity and mortality accounted by a single pathogen. Despite all the efforts to develop a new vaccination strategy it seems difficult in the near future to combat the threat posed by Mtb and it is further worsened by the emergence of multi-drug resistant form. The introduction of the Phenotypic noise and its understanding in the TB disease progression and establishment will be crucial in addressing the challenges posed by the Mtb. The phenotypic noise is believed to be a crucial factor in the in the pathogenesis of Salmonella typhimurium and EPEC. We have characterized the noisy expression of numerous proteins in the Mycobacterium marinum with varied functions. Among them, the EspH is one such protein that belongs to the extRD1-region, and is involved in regulation of Esx-1 secretory apparatus coded by the RD1-region. It also regulates the expression of another protein TlyA that may function as an inflammatory molecule. Therefore, to ascertain the role of EspH in M. marinum infection, the EspH immunized mice were challenged with M. marinum infection. It is observed that the EspH immunization is able to limit the bone damage caused by the M. marinum to the tail bone. However, the soft tissue surrounding the coccygeal vertebrae has been severely infected and the severity of the developed lesions was significantly enhanced. These observations suggest that the immunization is leading to pathological symptoms that are akin to acute phase of infection. Possibly the noisy expression of EspH protein might help the bacterium in balancing the expression of phenotypes responsible for virulence.