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Time-to-positivity in mycobacterial growth incubator tubes as a marker for bacterial subpopulations

Terrmin

HT25

Beskrivning

Mycobacterium tuberculosis (Mtb) can exist in a multitude of states, e.g. fast-growing with high metabolic activity or slow-growing/resting/dormant/persistent with low metabolic activity, extracellularly or inside macrophages, in hypoxic environment in caseous lung lesions, etc. These bacterial subpopulations are thought to have differential sensitivity to antimicrobial drugs, and lingering drug-tolerant dormant bacteria may be a cause for relapse to active disease after finalized treatment.

Currently, there is a lack of effective methods to differentiate bacterial subpopulations from each other. Proposed methods are relatively labor intensive and require expensive material or specialized infrastructure, meaning that they are difficult to use in routine clinical settings. The goal is to obtain similar information from metrics that are already widely used for clinical trials and treatment monitoring (like colony-forming units (CFU) and time-to-positivity (TTP)). By better understanding the properties of the TTP metric in relation to bacterial subpopulations in a sample, we could potentially deduce information about the proportion of resting bacteria. Shorter TTP generally indicates higher mycobacterial load in the original sample. It is possible to read out not only the TTP but the continuous curve of growth units recorded from inoculation and forward. By interpreting the shape of the growth unit (GU) curve, the relation between bacterial numbers and state, growth rates and delays can be elucidated.

This analysis could potentially contribute to optimized treatment of Mtb by having better information on the bacterial subpopulations and thereby also their sensitivity to antimicrobial drugs.

The work will be carried out in Uppsala, however in a research group, that offers an international environment. The working language will be mainly English.

Does this project sounds like something for you? Apply here or contact the supervisor (see below) or Maria Kjellsson (maria.kjellsson@uu.se) if you have additional questions. We look forward to your application!

Huvudområde

Farmaceutisk vetenskap

Ämne

Farmakometri

Typ

Beräkningsstudie

Företag

Uppsala University

Ort/Plats

Uppsala

Handledarens namn

Milena Boczar och Elin Svensson

Handledarens e-post

milena.boczar@uu.se, elin.svensson@uu.se

Institution

Institutionen för farmaci

Program

Masterprogram i läkemedelsutveckling

Kurs

Degree project in Drug Discovery and Development 45 c - 3FK044

Omfattning/hp

45hp