The German cockroach, Blattella germanica, is the most common pestiferous cockroach species in human
environments. B. germanica contributes to the transmission of bacteria that cause enteric (diarrheal) disease,
including Salmonella enterica serovar Typhimurium, but the mechanisms of transmission are not well
understood. Enteric bacterial pathogen transmission by cockroaches has previously been described as
mechanical in nature. Mechanical transmission is a passive, non-replicative transfer of bacteria from one location
or host to another. This mechanism is limited in impact relative to active biological transmission. However, recent
data from our laboratory indicate that transmission of S. Typhimurium by German cockroaches is markedly more
complex than simple mechanical transmission and instead resembles biological transmission by other insects
that intake bacteria from infected hosts and are subsequently colonized, enabling active and prolonged shedding
and transmission. In particular, we have observed that following ingestion, S. Typhimurium undergoes a lifestyle
change and multiple replication events in the digestive tract of the German cockroach. Furthermore, we have
identified several S. Typhimurium genes that are necessary for bacterial colonization and shedding from the gut
of B. germanica, evidencing an active role of the bacteria. The central objective of the proposed research project
is to gain a detailed understanding of the mechanisms of biological vector-borne transmission of S. Typhimurium
by the German cockroach. Three independent specific aims are proposed. First, we will elucidate the fine
spatiotemporal details of wild-type S. Typhimurium colonization and shedding in nymph and adult cockroaches.
Second, leveraging an unparalleled array of mutant S. Typhimurium strains, we will identify specific bacterial
genes and functions that are necessary for colonization of cockroaches and subsequent transmission. Third, we
will determine the effects of two key host factors, namely antimicrobial effectors and the gut microbiota, on S.
Typhimurium colonization and shedding. Together, the proposed studies will establish a picture of how bacterial
and host factors interact to shape biological transmission of S. Typhimurium by the German cockroach, providing
fundamental insight into the dynamics of a unique, poorly studied vector-pathogen system with a global
distribution and public health impact.