Souvik Bhattacharyya, PhD

Areas of Interest

Research Interests

Background: We study how various transient forms of bacterial behavior impact the evolution of antimicrobial resistance (AMR), a global health concern projected to cause approximately 10 million deaths annually by 2050. Bacteria are rapidly developing genetic resistance to existing antimicrobials, depleting our arsenal of effective drugs. Therefore, it is critical that we not only develop new antibiotics but also implement therapeutic strategies to slow down the evolution of AMR in clinical settings.

Well-known genetic mechanisms of AMR include genes or mutations that inactivate antibiotics, modify their targets, and increase efflux or decrease influx. Transient bacterial behaviors like necrosignaling, memory, tolerance, heterogeneity, persistence, swarming, and biofilm formation, accelerate AMR evolution by promoting survival under antibiotic pressure and acquiring genetic resistance. The interplay between these stress responses and AMR emergence is underexplored, thus therapeutic strategies against AMR evolution is virtually non-existent.

Previous Work: Souvik has a long-standing interest in molecular evolution and microbial behavior. He studied how various ingenious survival strategies of bacteria can impact the evolution of antibiotic resistance. His work led to the discovery of ‘necrosignaling,’ where bacterial cells killed by antibiotics release a danger signal that warns live cells. He recently discovered that E. coli cells have a deterministic iron memory that affects their behavior on a surface and their survival in the presence of antibiotics. He aims to create ‘Evolutionary Therapeutics’ to combat antimicrobial resistance evolution in the real world.

Current Work: Our research program combines genetics, molecular biology, evolution, genomic database analyses, mathematical modeling, and systems approaches and aims to elucidate mechanisms that accelerate AMR evolution. Our long-term ambition is that our research findings form the basis for the development of next-generation therapeutic strategies that eliminate bacterial pathogens, while also targeting the emergence of AMR.

Currently, we are working on several projects within this broad field.

1. Phenotypic vulnerabilities of AMR strains: We aim to identify new drug targets by exploiting the phenotypic defects that antibiotic-resistance mutations create. The antibiotics target essential functions of the cell, and so resistant mutations in these genes critically affect these essential functions thus making bacteria vulnerable. In other words, certain genes that are not essential in an antibiotic-sensitive strain, becomes essential in a resistant strain. The goal of this project is to identify them using modern genetic tools.
2. Necrosignaling: Recently, we discovered the phenomenon of necrosignaling, where bacterial cells killed by antibiotics release a danger signal for live cells. This has implications for clinical antibiotics research since, akin to quorum sensing, perturbing necrosignals could be used to impede the capacity of bacteria to tolerate antimicrobial treatment. It is therefore important to identify potential necrosignaling modules in diverse species that are clinically significant. We aim to identify necrosignals in other bacteria and its clinical significance.
3. Bacterial Memory in Antibiotic Resistance: In humans, repeated encounters with a wide variety of stimuli can reactivate specific neurons to produce long-term memories. We recently showed that a multigenerational memory exists in E. coli swarming motility, where bacteria “remember” their swarming experience for several generations. The molecular basis of this memory is the levels of available cellular iron and controls surface behavior, antibiotic survival, and biofilm formation. We aim to find the exact molecular mechanism of this phenomenon and its prevalence across different species in diverse settings.
4. Effect of Global Warming on AMR: Unpublished data from our lab has shown that surface moisture can impact mutation rates in surface-dwelling bacteria. The recent rise in global temperatures has indicated an increase in humidity and surface moisture. Global warming has also been linked to the rise of antibiotic resistance. We aim to test if global warming-like fluctuations in temperature and humidity would increase mutation rates in bacteria.

Publications