|Home | About | Journals | Submit | Contact Us | Français|
Despite significant progress in understanding the biology of minimal self-replicating organisms, limited information regarding the factors that are involved in their virulence and host tropism is available. Using the ruminant pathogen Mycoplasma agalactiae as a model system, Baranowski et al. (p. 1542-1551) identified genomic regions that were specifically required for mycoplasma proliferation upon cocultivation with mammalian cells, while being dispensable for axenic growth. This study raises questions regarding essential gene sets in minimal organisms and provides a means for addressing this issue at a higher level of complexity, the host cell context.
Staphylococcus aureus is exposed to a variety of environmental stressors within the mammalian host, including iron paucity. As with many bacterial pathogens, S. aureus senses iron levels via the ferric uptake regulator (Fur) to regulate the expression of iron uptake systems. Torres et al. (p. 1618-1628) demonstrate that S. aureus Fur also coordinates the differential expression of secreted virulence factors. Disruption of fur attenuates S. aureus infection in vivo, a phenotype partially due to the decreased production of immunomodulatory proteins involved in the inhibition of neutrophil recruitment and neutrophil-mediated killing. Taken together, these results identify iron sensing as a new strategy exploited by S. aureus to combat host defense systems.
Candida albicans is a major agent of opportunistic infections among immunocompromised patients. The ultimate challenge in C. albicans antifungal therapy is to identify novel targets to improve protective host responses to invasive candidiasis. Galán-Díez et al. (p. 1426-1436) show that Cek1 mitogen-activated protein kinase (MAPK) blockade in C. albicans causes cell wall β-glucan unmasking and renders the fungus “visible” to the pathogen recognition receptor dectin-1. This study demonstrates that CEK1 disruption enhances dectin-1-mediated immune responses, including binding, phagocytosis, killing, and the activation of intracellular signaling pathways on human phagocytes exposed to the cek1 mutant. Consequently, drugs targeting this fungus-conserved MAPK may provide new tools for fighting fungal infections.
Studies with patients and animal models of sepsis have revealed that changes in the immune response during sepsis play a decisive role in outcome. Muenzer et al. (p. 1582-1592) use a clinically relevant mouse model of cecal ligation and puncture (CLP) followed by Pseudomonas aeruginosa pneumonia to characterize these changes. Susceptibility to Pseudomonas aeruginosa pneumonia following CLP was dependent upon timing of secondary injury and was associated with an immunosuppressive phenotype. Furthermore, through the administration of the immune modulator AS101, Muenzer et al. were able to alter the immune response and improve survival from secondary pneumonia.
The ability to alter the microbial community structure within the intestine is poorly understood. It has been hypothesized that the gut microbiota are stable and not susceptible to dramatic perturbation. Bailey et al. (p. 1509-1519) utilize bacterial tag-encoded FLX amplicon pyrosequencing and report that exposing mice to stressful stimuli can significantly change the community structure of the cecal microbiota. Changes in the cecal microbiota were associated with increased colonization by Citrobacter rodentium after oral challenge. Although the stress response is often immunosuppressive, measures of the mucosal and lymphatic immune responses, as well as cytokine gene expression, were either enhanced or not affected by the stressor. Thus, this study demonstrates for the first time that stress may render a host more susceptible to infection through perturbation of the microbial community structure.
There is accumulating evidence that oral bacteria can infect the pregnant uterus, causing adverse pregnancy outcomes. However, the extent to which the oral microbiome is implicated in intrauterine infection has not been determined. Fardini et al. (p. 1789-1796) systematically examined oral bacteria capable of hematogenous transmission to the placenta in pregnant mice. A diverse group of oral species, most of which have been associated with adverse pregnancy outcomes in humans, were identified, although the source of infection was unknown. This study identifies the oral microbiome as a previously unrecognized source of intrauterine infection.