|Abstract||Anthrax is an infectious disease caused by Bacillus anthracis, which is a spore forming bacterium. Even though the anthrax toxins and capsule, encoded on 2 plasmids pXO1 and pXO2, play crucial role in the pathogenesis of anthrax infection, evidence suggests that chromosomal genes also play a role. The ClpX ATPase was discovered to be crucial for B. anthracis virulence via protection against host antimicrobial peptides. In this study, we want to investigate the role of ClpATPase family members in regulation of stressors including acidic stress, temperature stress, salt stress, and non-cell/cell envelope active antibiotics. We found that clpX is necessary for survival in an acidic environment and growth under heat stress. We demonstrate that acidic stress resistance is mediated by the formation of the ClpXP protease using a ClpX complementation plasmid that is incapable of interacting with ClpP. There is no association between clpX with other stressors. Additionally, we genetically disrupted other Clp ATPase in B. anthracis, ClpB and ClpC, to study its role in the regulation of stress responses. Unfortunately, we was not successful in constructing the insertional knock-out ClpC to study its role. We discovered that clpB is necessary for growth under heat stress. Acidic stress, salt stress, antibiotics have no association with clpB. We conclude that the ClpX ATPase is required for B. anthracis pathogenicity via defenses against host antimicrobial peptides and for survival in an acidic environment. Understanding the role of members of the Clp ATPase family in the regulation of stress responses will ultimately infer us with more targets for either directly combating infection or improving the efficacy of already available medicines.