Mechanisms of Bacterial Colonization of the Respiratory Tract

Abstract

Respiratory tract infections are an important cause of morbidity and mortality worldwide. Chief among these are infections involving the lower airways. The opportunistic bacterial pathogens responsible for most cases of pneumonia can cause a range of local and invasive infections. However, bacterial colonization (or carriage) in the upper airway is the prerequisite of all these infections. Successful colonizers must attach to the epithelial lining, grow on the nutrient-limited mucosal surface, evade the host immune response, and transmit to a susceptible host. Here, we review the molecular mechanisms underlying these conserved stages of carriage. We also examine how the demands of colonization influence progression to disease. A range of bacteria can colonize the upper airway; nevertheless, we focus on strategies shared by many respiratory tract opportunistic pathogens. Understanding colonization opens a window to the evolutionary pressures these pathogens face within their animal hosts and that have selected for attributes that contribute to virulence and pathogenesis.

Keywords: Streptococcus pneumoniae; commensal; inflammation; nasopharynx; opportunistic pathogen.

Figure 1

The essential stages of colonization of the upper respiratory tract are presented here as a cycle. Colonizing bacteria (brown) enter the nasopharyngeal lumen and pass through the mucous layer (blue), in part facilitated by their capsule. Next, bacteria reach the epithelial surface and bind loosely and tightly to host surface carbohydrates and proteins, respectively. Bacteria obtain nutrients by exploiting host inflammation (through, for example, digestion of sialylated mucins) and evading nutritional immunity. These nutrients allow for microbial replication; persistence also involves evasion of host immune responses, both humoral (through IgA1 protease) and cellular. Opportunistic pathogens exploit these responses to drive transmission by exiting the host, and the same factors that allow for increased colonization and transmission predispose to invasion of host barriers, potentially a strategy for persistence.