Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), infects 1.7 billion people worldwide. Each year, 2-3 million will eventually die of TB. With the discovery of effective anti-tuberculosis drugs, TB became curable. However, Multi Drug Resistant TB and the recent appearance of extensive drug resistant TB, which in many cases is untreatable, has the potential to make TB an incurable disease once again. The TB epidemic has been worsened by HIV/AIDS. Factors involved in the regulation of many phenotypes of MTB such as virulence, latency, antibiotic resistance and ability to survive under harsh conditions are not well understood. Bacterial cell density dependent signaling (quorum sensing), discovered three decades ago, has been shown to play a major role in the control of virulence, sporulation, antibiotic production, resistance to harsh conditions, cell division, biofilm development and drug resistance in bacteria. Data on the role of quorum sensing on the regulation of MTB phenotypes are limited. The isolation and characterization of genes involved in quorum sensing offer a novel approach in understanding and modifying bacterial physiology. In the proposed study, our broad objective is to identify and characterize genes involved in cell-to-cell signaling in mycobacteria. The specific objectives include: (1) To use genetic techniques to study the role of the Rhomboid-like proteins in the physiology of mycobacteria. This will be achieved by inactivation of rhomboid like genes (quorum sensing genes in other organisms) in M. smegmatis and determining how this affects signal production, morphology, survival and other phenotypes of mycobacteria. (2). To construct a library of quorum sensing regulated gene fusions in mycobacteria. This objective will identify the mycobacterial genes whose regulation is cell density dependent. This will be addressed through construction of random lacZ reporter transcriptional gene fusions in M. smegmatis chromosome. (3) To examine the regulatory pathways of the quorum sensing regulated gene fusions in mycobacteria. This will be achieved through screening for other genes that alter the expression of quorum sensing regulated lacZ gene fusions identified in objective 2. This study will provide further information on quorum sensing regulated mycobacterial functions and also describe the regulatory pathways. This will enrich our knowledge on mycobacterial biology and may reveal novel drug and vaccine targets.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZAI1-GSM-M (M1))
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Jacobs, Gail G
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Makerere University
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Kateete, David P; Nakanjako, Ritah; Okee, Moses et al. (2017) Genotypic diversity among multidrug resistant Pseudomonas aeruginosa and Acinetobacter species at Mulago Hospital in Kampala, Uganda. BMC Res Notes 10:284
Kateete, David P; Nakanjako, Ritah; Namugenyi, Juliet et al. (2016) Carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii at Mulago Hospital in Kampala, Uganda (2007-2009). Springerplus 5:1308
Wampande, Eddie M; Mupere, Ezekiel; Jaganath, Devan et al. (2015) Distribution and transmission of Mycobacterium tuberculosis complex lineages among children in peri-urban Kampala, Uganda. BMC Pediatr 15:140
Wampande, Eddie M; Hatzios, Stavroula K; Achan, Beatrice et al. (2015) A single-nucleotide-polymorphism real-time PCR assay for genotyping of Mycobacterium tuberculosis complex in peri-urban Kampala. BMC Infect Dis 15:396
Ezati, Nicholas; Lukoye, Deus; Wampande, Eddie M et al. (2014) The Mycobacterium tuberculosis Uganda II family and resistance to first-line anti-tuberculosis drugs in Uganda. BMC Infect Dis 14:703
Kateete, David Patrick; Kabugo, Usuf; Baluku, Hannington et al. (2013) Prevalence and antimicrobial susceptibility patterns of bacteria from milkmen and cows with clinical mastitis in and around Kampala, Uganda. PLoS One 8:e63413
Wampande, Eddie M; Mupere, Ezekiel; Debanne, Sara M et al. (2013) Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease. BMC Infect Dis 13:484
Okee, Moses S; Joloba, Moses L; Okello, Margaret et al. (2012) Prevalence of virulence determinants in Staphylococcus epidermidis from ICU patients in Kampala, Uganda. J Infect Dev Ctries 6:242-50
Kateete, David Patrick; Katabazi, Fred Ashaba; Okeng, Alfred et al. (2012) Rhomboids of Mycobacteria: characterization using an aarA mutant of Providencia stuartii and gene deletion in Mycobacterium smegmatis. PLoS One 7:e45741
Dickman, Katherine R; Nabyonga, Lydia; Kateete, David P et al. (2010) Detection of multiple strains of Mycobacterium tuberculosis using MIRU-VNTR in patients with pulmonary tuberculosis in Kampala, Uganda. BMC Infect Dis 10:349

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