Bacterial differentiation, development, and disease: mechanisms for survival

Abstract

Bacteria have the exquisite ability to maintain a precise diameter, cell length, and shape. The dimensions of bacteria size and shape are a classical metric in the distinction of bacterial species. Much of what we know about the particular morphology of any given species is the result of investigations of planktonic cultures. As we explore deeper into the natural habitats of bacteria, it is increasingly clear that bacteria can alter their morphology in response to the environment in which they reside. Specific morphologies are also becoming recognized as advantageous for survival in hostile environments. This is of particular importance in the context of both colonization and infection in the host. There are multiple examples of bacterial pathogens that use morphological changes as a mechanism for evasion of host immune responses and continued persistence. This review will focus on two systems where specific morphological changes are essential for persistence in animal models of human disease. We will also offer insight into the mechanism underlying the morphological changes and how these morphotypes aid in persistence. Additional examples of morphological changes associated with survival will be presented.

Keywords: morphology; otitis media; persistence; urinary tract infection.

Figure 1

UPEC intracellular differentiation pathway. UPEC (maroon rods) invade into the cytoplasm of the bladder epithelial cell to initiate the intracellular developmental and differentiation pathway (early IBC). The epithelial cell becomes engorged with UPEC in the coccoid (dark maroon) and filamentous (light maroon) morphologies to form the pod (intracellular differentiation). The pod ultimately lyses, releasing rod and filamentous morphotypes that invade into neighboring naïve cells for persistence (egress and second generation IBC).

Figure 2

NTHI differentiation in response to fluctuations in nutritional availability. NTHI IBC formation is dependent upon the nutritional state at the time of infection. Continuously exposed to heme-iron (dark brown rods) form mat-like biofilms on the epithelial surface with limited intracellular development. In contrast, restricted for heme-iron (light brown rods) form a biofilm on the surface that has an open architecture containing filamentous NTHI. In addition, heme-iron restricted NTHI responded to nutritional limitation by forming IBCs within the epithelial cells.