Our research is focused on two aspects broadly related to bacterial physiology and pathogenesis:
Adaptive strategies of bacteria to nutrient starvation
Conditions that sustain constant bacterial growth are seldom found in nature. Bacterial growth is often limited by availability of nutrients; soil, water, and even host environments such as macrophages can lack essential nutrients to support growth. Hence, many bacteria spend the majority of their time in states of little or no growth because they are starved of essential nutrients. The nutrient-starved and growth-attenuated state is now widely considered as an important physiological state in bacterial pathogenesis and survival. We use nitrogen starvation as a model nutrient stress to study the temporal changes in the transcriptome of Escherichia coli during sustained nitrogen starvation, the regulatory basis underpinning these changes and the consequences of their dysregulation to bacterial tolerance to antibacterial stresses and survival.
Host(ile) Takeover strategies of phages
Phages have evolved diverse and sophisticated mechanisms to take-over essential host processes to facilitate the successful development of phage progeny. Many such host takeover mechanisms involve small proteins that interact with and repurpose, inhibit or modulate the activity of essential bacterial enzymes, which as a consequence, often result in the demise of the bacterial cell. We study the phage-encoded antibacterial small proteins and their bacterial targets at a molecular level not only to unravel new phage biology, but also to inform and inspire the discovery of novel antibacterial strategies.
et al., 2019, Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein., Journal of Biological Chemistry, ISSN:0021-9258
et al., 2019, Xenogeneic regulation of the bacterial transcription machinery, Journal of Molecular Biology, ISSN:0022-2836
Switzer A, Brown D, Wigneshweraraj S, 2018, New insights into the adaptive transcriptional response to nitrogen starvation in Escherichia coli, Biochemical Society Transactions, Vol:46, ISSN:0300-5127, Pages:1721-1728
et al., 2018, Naturally occurring polymorphisms in the virulence regulator Rsp modulate Staphylococcus aureus survival in blood and antibiotic susceptibility, Microbiology, Vol:164, ISSN:1350-0872, Pages:1189-1195
et al., 2018, A novel regulatory factor affecting the transcription of methionine biosynthesis genes in Escherichia coli experiencing sustained nitrogen starvation, Microbiology, Vol:164, ISSN:1350-0872, Pages:1457-1470