Combating bacterial infections in the critically injured patients has become increasingly difficult due to the rapid emergence of multi-drug resistant bacterial strains. Depression of host defense mechanisms coupled with the need for invasive procedures disproportionately increase the risk of nosocomial infections. In the last three decades, no new class of antibiotics has been discovered that does not allow emergence of multi-drug resistance. Much of our research on bacterial infections has been focused on either antibacterial therapy to eradicate the infection or on attempts to reverse observed changes in host immunity due to systemic infection. The later strategy has proven to be ineffective in clinical trials of sepsis. Much of the predicament we find ourselves in treating sepsis stems from limited appreciation of the genetic and biochemical changes made by the pathogen in response to host immunity. The research focus of Dr. Shankar’ s laboratory is to study how mammalian immune system responds to the specific virulence genes and gene products of the pathogen. Dr. Shankar and his collaborators are developing several Pseudomonas aeruginosa and Acinetobacter baumannii strains that lack various virulence-associated genes and reconstituted bacteria where the specific gene product is replaced. Using these bacterial strains his laboratory is attempting to understand the relationship between host cellular responses and specific gene products of the pathogen. Through these approaches, a strong correlation between specific bacterial virulence gene(s) and specific set(s) of host immune responses can be made. Ultimately, the knowledge gained through this research can lead to reliable diagnostics and to targeted and novel antibacterial therapies.