Pangenome Analysis Reveals Novel Contact-Dependent Growth Inhibition System and Phenazine Biosynthesis Operons in Proteus mirabilis BL95 That Are Located in An Integrative and Conjugative Element.

Proteus mirabilis is a leading cause of urinary tract infections and a common commensal of the gastrointestinal tract. Our recent study (JB) showed that P. mirabilis strain BL95 employs a novel contact-dependent killing system against enteric bacteria in the mouse gut and in vitro. To uncover the genetic determinants of this system, we performed whole-genome sequencing of BL95 and compared it with 98 complete genomes of P. mirabilis. BL95 carries 56 coding sequences (CDSs) not found in other P. mirabilis. Over half of these unique genes are located on a novel integrative conjugative element (ICE) named ICEPm2, inserted in tRNA-Phe and exclusive to BL95. ICEPm2 has integration, conjugation, and DNA replication modules nearly identical to ICEPm1 (common in P. mirabilis), but ICEPm2 of BL95 carries two unique operons for P. mirabilis-a phenazine biosynthesis and a contact-dependent growth inhibition (CDI) system. ICEPm2 is absent in the P. mirabilis (AR_0156) closest to BL95 and it is present in the genomes of several Escherichia coli from mouse intestines, indicating its recent horizontal mobilization. BL95 shares over 100 genes of five different secretion systems with other P. mirabilis, mostly poorly studied, making a large pool of candidate genes for the contact-dependent growth inhibition

Environmental Dimensionality Controls the Interaction of Phagocytes with the Pathogenic Fungi Aspergillus fumigatus and Candida albicans

The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why “delocalized” Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Siderophore-Mediated Zinc Acquisition Enhances Enterobacterial Colonization of the Inflamed Gut

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the pH increases. Thus, our results indicate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to commensal and pathogenic Enterobacteriaceae

Siderophores: More than Stealing Iron.

Siderophores are small molecular iron chelators that are produced by microbes and whose most notable function is to sequester iron from the host and provide this essential metal nutrient to microbes. Recent studies have proposed additional, noncanonical roles for siderophores, including the acquisition of noniron metals and modulation of host functions. Recently, Holden et al. (V. I. Holden, P. Breen, S. Houle, C. M. Dozois, and M. A. Bachman, mBio 7:e01397-16, 2016, http://dx.doi.org/10.1128/mBio.01397-16) showed that siderophores secreted by Klebsiella pneumoniae during lung infection induce stabilization of the transcription factor HIF-1α, increase the expression of proinflammatory cytokines in the lung, and promote dissemination of K. pneumoniae to the spleen. Thus, their study demonstrated novel roles for siderophores in vivo, beyond iron sequestration. The interaction of siderophores with host cells further promotes the pathogenicity of K. pneumoniae and is likely relevant for other pathogens that also secrete siderophores in the host

Neglected gut microbiome: interactions of the non-bacterial gut microbiota with enteric pathogens

ABSTRACTA diverse array of commensal microorganisms inhabits the human intestinal tract. The most abundant and most studied members of this microbial community are undoubtedly bacteria. Their important role in gut physiology, defense against pathogens, and immune system education has been well documented over the last decades. However, the gut microbiome is not restricted to bacteria. It encompasses the entire breadth of microbial life: viruses, archaea, fungi, protists, and parasitic worms can also be found in the gut. While less studied than bacteria, their divergent but important roles during health and disease have become increasingly more appreciated. This review focuses on these understudied members of the gut microbiome. We will detail the composition and development of these microbial communities and will specifically highlight their functional interactions with enteric pathogens, such as species of the family Enterobacteriaceae. The interactions can be direct through physical interactions, or indirect through secreted metabolites or modulation of the immune response. We will present general concepts and specific examples of how non-bacterial gut communities modulate bacterial pathogenesis and present an outlook for future gut microbiome research that includes these communities