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mohammad tabish ahmed - eTheses Repository - University of ...

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Chapter 6<br />

Section 6.1: Testing the ability <strong>of</strong> M. tuberculosis Cpn60.1 to function in M.<br />

smegmatis<br />

Background<br />

As discussed in the introductory chapter and in chapter 3, it is known that the main housekeeping<br />

chaperonin in both M. tuberculosis and M. smegmatis is Cpn60.2, while Cpn60.1 has<br />

evolved to perform alternate functions.<br />

Our current understanding <strong>of</strong> the functions <strong>of</strong><br />

MsCpn60.1 implicates its role in bi<strong>of</strong>ilm maturation for M. smegmatis while the MtbCpn60.1<br />

chaperonin has been shown to play a role in granuloma formation during tuberculosis (Hu et<br />

al., 2008, Kim et al., 2003, Ojha et al., 2005).<br />

Bi<strong>of</strong>ilm formation is an important aspect <strong>of</strong> many pathogenic bacteria, including E. coli, V.<br />

cholerae, H. influenze, and P. aeroginosa (Hall-Stoodley & Stoodley, 2009, Bjarnsholt et al.,<br />

2010, Fux et al., 2005). These bacteria make use <strong>of</strong> the bi<strong>of</strong>ilms to provide them with<br />

protection from the diverse environmental and nutrient conditions, while also providing them<br />

with the means to protect themselves from the effects <strong>of</strong> antibiotics (Bjarnsholt et al., 2010,<br />

Hall-Stoodley et al., 2004, Cernohorska & Votava, 2010).<br />

In M. smegmatis, it has been shown that the loss <strong>of</strong> bi<strong>of</strong>ilm maturation can be caused by<br />

deleting the groEL1 (Mscpn60.1) gene which results in the lack <strong>of</strong> association between<br />

MsCpn60.1 and KasA (Ojha et al., 2005). KasA is a component <strong>of</strong> the fatty acid synthase<br />

(FAS)-II complex which is required for the elongation <strong>of</strong> mycolic acid chains. So the deletion<br />

209

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