Overview
Transmission is a critical component in the life cycle of any successful pathogen and can be considered as the first step towards the carrier- and the disease state. However, it is also one of the least characterized steps because of the inherent complexities in studying natural transmission. Therefore, our lab aims to provide insight into the bacterial or host factors associated with mucosal colonization, pathogen-microbiota interactions, and host-to-host transmission. Understanding these intricate processes would allow us new avenues to block the manifestation of the disease state.
Research Interest
Our laboratory utilizes diverse methods that blend bacterial genetics, animal models, and molecular, biochemical, and genome-wide approaches to broaden our understanding of mucosal colonization and host-to-host transmission of bacterial pathogens. Our colonization and transmission studies are carried out by employing two medically notable bacterial pathogens-Klebsiella pneumoniae (Kpn) and Streptococcus pneumoniae (Spn).
Klebsiella pneumoniae (Kpn)
Antimicrobial resistance is now considered a public health crisis. In the United States alone, over 2 million people are infected with antibiotic-resistant bacteria, of which over 23,000 succumb to their infections. For this reason, both the World Health Organization (WHO) and the Centers for Disease Control (CDC) have labeled fighting antimicrobial resistance a “public health priority.” K. pneumoniae, a gram-negative, highly antibiotic-resistant bacterium, is one of the leading causes of hospital-acquired infections. It readily colonizes the mucosal surfaces of humans and animals and is highly transmissible in a hospital setting.
The emphasis of most studies tends to be on Kpn-associated disease states. Our novel approach included the development of a novel murine model of Kpn gastro-intestinal colonization and host-to-host transmission occurring through the fecal-oral route. Epidemiological studies have demonstrated that gut colonization of the host is the first step before disease manifestations arise at distal sites. Using our animal model, we are identifying and defining the role of bacterial and host determinants, including interactions with the resident gut microbiome that contribute towards Kpn’s pathogenesis.
Streptococcus pneumoniae (Spn)
Pneumococcus remains one of the leading causes of morbidity and mortality in young children, older adults, and the immune-compromised worldwide. Spn colonizes the mucosal surface of the upper respiratory tract of its obligate human host. From this site, Spn can disseminate to other locations within the host and cause disease manifestations. The advent of the pneumococcal conjugate vaccine (PCV) led to a massive reduction in the total number of cases. However, even with the availability of this and other vaccines, the number of acute disease cases is still considerably high, with over half a million deaths recorded in children under the age of 5.
Pneumococcus is highly transmissible with a concurrent viral infection, especially in crowded settings such as daycare centers. To study pneumococcal colonization and transmission, we developed an infant mouse model that recapitulates many essential human transmission requirements (proximity, occurring in the young, and high transmission rates with viral co-infection). We have used this model to identify the de novo transcriptional changes during colonization of the upper respiratory tract (URT). Pneumococcal gene regulation in the URT remains poorly understood, and we aim to identify bacterial and host factors that drive Spn transcriptional modulations that determine its success.