Practice Question #14 p. 225Knowing the pathogenesis of TB, what virulence factors would you expect to see in thismicroorganism at each stage (main steps) of pathogenesis?Find the categories of molecules and their function in TB pathogenesis for eachtheoretical infection stage as seen in class (exposure, adherence,.)Steps to pathogenesisMultiple events, each a limiting barrier for infection, need to occurbefore a full-fledged bacterial infections translate into symptomsand pathology.The infection processThe disease processТOXICITYToxin effectsare local orsystemicEXPOSUREADHERENCEto skin or mucosaINVASIONMULTIPLICATIONGrowth and productionof virulence factorsand toxinsTISSUE ORSYSTEMIC DAMAGEto pathogensthrough epitheliumINVASIVENESSFurther growthat original anddistant sitesBreak in barrier It was important for Lilly to understand how the bacteria were able to cause disease in patients.The mechanism of pathogenesis by M. tuberculosis starts in the lung alveoli. The cell wall of M.tuberculosis allows it to resist phagocytolysis by the alveolar macrophages, where they canmultiply. They can then induce apoptosis in macrophages, which die, and the bacteria is free toinfect other macrophages. As the cycle of infection slowly progresses, the body's response to theinfection is to try to wall off the bacteria in granulomas (wall of immune cells, both dead and alive,surrounding the bacteria to restrict its spread). Eventually, the bacteria can escape the granulomaand infect other parts of the lung.Transmission of MtbInitial infection andGranuloma cavitationyreplication of Mtbin macrophagesand disseminationof Mtb in the lungInfectedmacrophagesCaseatinggranulomaRecruitment ofInnate andadaptive immunecellsInfected cells undergonecrosis resulting inthe formation of the caseumSolid granuloma,containment of MtbFigure 6. Granuloma development during TB progression. The initial stages of TB infectioninvolve inhalation of M. tuberculosis (Mtb) bacilli into the lung and phagocytosis by residentalveolar macrophages. Mtb can survive phagocytosis and grow within macrophages for a while.Once their number reaches a certain threshold and the bacteria has spread locally to othermacrophages, they can elicit a local inflammatory response resulting in the recruitment ofmonocytes and macrophages and other immune cells to the site of infection, resulting in theformation of a granuloma around the infectious agent. This is the balanced solid state in whichmany granulomas persist and restrict the bacilli at their center. However, as the disease progresses,increased necrotic breakdown of granuloma cells leads to the accumulation of caseum (cheese-likeloose collection of dead and live cells), which may result in cavitation of granulomas. Ultimately,as the granuloma cavitates and collapses into the lung, Mtb bacilli are released into the airway andcan spread to other parts of the lung.

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Virulence factors are bacteria-associated compounds that are essential for a bacterium to cause…