Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in “host” susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3γ and Reg3β, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter “host” resistance, and a novel means to alter enteric infection and to study host-pathogen interactions.

Directional growth is a function of polarized cells such as neurites, pollen tubes, and fungal hyphae. Correct orientation of the extending cell tip depends on signaling pathways and effectors that mediate asymmetric responses to specific environmental cues. In the hyphal form of the eukaryotic fungal pathogen Candida albicans, these responses include thigmotropism and galvanotropism (hyphal turning in response to changes in substrate topography and imposed electrical fields, respectively) and penetration into semisolid substrates. During vegetative growth in C. albicans, as in the model yeast Saccharomyces cerevisiae, the Ras-like GTPase Rsr1 mediates internal cellular cues to position new buds in a prespecified pattern on the mother cell cortex. Here, we demonstrate that Rsr1 is also important for hyphal tip orientation in response to the external environmental cues that induce thigmotropic and galvanotropic growth. In addition, Rsr1 is involved in hyphal interactions with epithelial cells in vitro and its deletion diminishes the hyphal invasion of kidney tissue during systemic infection. Thus, Rsr1, an internal polarity landmark in yeast, is also involved in polarized growth responses to asymmetric environmental signals, a paradigm that is different from that described for the homologous protein in S. cerevisiae. Rsr1 may thereby contribute to the pathogenesis of C. albicans infections by influencing hyphal tip responses triggered by interaction with host tissues.The growth and behavior of living cells is achieved by a process of vectorial metabolism in which growth is directed or restricted to specific cellular locations under the influence of endogenous and exogenous signals and stimuli. For example, in the model yeast Saccharomyces cerevisiae, budding yeast cell growth involves polarization in a direction that is prescribed by proteins that provide internal cues. These proteins include cortically localized bud-site selection proteins that recruit and activate the major polarity establishment Rho GTPase Cdc42 either adjacent to or directly opposite the site of emergence by the previous daughter cell (12, 13). In contrast to the case for budding cells in S. cerevisiae, where positional landmarks are internal, pheromones provide mating yeast cells with extracellular signals that override the internal cues so that the growth of the mating projection (shmoo) is oriented in the direction of the putative mating partner (13).During yeast cell growth in Candida albicans, an opportunistic fungal pathogen of humans, the direction of polarity establishment is controlled, as it is in S. cerevisiae, by internal cues at the mother cell cortex (23,30,57,64). C. albicans also grows in a filamentous hyphal morphology that is not exhibited by S. cerevisiae. Understanding how hyphal morphogenesis occurs and is regulated has generated a great deal of interest because the hyphal form of C. albicans has been associated with the invasion of host tissues and mortality (54,65).The hyphae of C. albicans and other human and plant fun...

Background: Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner.