A role for proteobacterial mammalian cell entry domains in phospholipid trafficking and infection

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Isom, Georgia Louise (2017). A role for proteobacterial mammalian cell entry domains in phospholipid trafficking and infection. University of Birmingham. Ph.D.

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Abstract

Mammalian cell entry (MCE) domains are so called due to the reported ability of an Escherichia coli strain harbouring the mce1 gene from Mycobacterium tuberculosis to invade mammalian cells. Bioinformatic analyses presented here demonstrated that proteins containing a single MCE domain are widespread in bacteria and that proteins containing multiple MCE domains are specific to and have evolved within Proteobacteria. Gene neighbourhood analyses revealed that MCE domain containing proteins are components of transporters and that multi MCE domain containing proteins constitute a novel type of transporter. E. coli was shown to harbour three MCE proteins: the single MCE domain protein MlaD and two multi-domain proteins PqiB and YebT. All three proteins were shown to locate to the inner membrane and bind phospholipids. Phenotypic studies revealed that their functions overlap but are distinct. Infection studies with Salmonella showed that the proteins are important for systemic infection but are not required for mammalian cell entry. Phospholipid growth experiments with Salmonella demonstrated that they are important for phospholipid uptake. These findings suggest that MCE domain containing proteins in Proteobacteria are not directly involved in mammalian cell entry and instead play a role in other aspects of mammalian infection related to phospholipid trafficking.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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