One potential outcome of the adaptive coevolution of humans and bacteria is the development of commensal relationships, where neither partner is harmed, or symbiotic relationships, where unique metabolic traits or other benefits are provided. Our gastrointestinal tract is colonized by a vast community of symbionts and commensals that have important effects on immune function, nutrient processing, and a broad range of other host activities. The current genomic revolution offers an unprecedented opportunity to identify the molecular foundations of these relationships so that we can understand how they contribute to our normal physiology and how they can be exploited to develop new therapeutic strategies.

https://science.sciencemag.org/content/sci/292/5519/1115.full.pdf

Commensal Host-Bacterial Relationships in the Gut

Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10-deficient (Il10(-/-)) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)-treated Il10(-/-) mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10(-/-) mice, without altering intestinal inflammation. Mucosa-associated pks(+) E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

/pdf/intestinal-inflammation-targets-cancer-inducing-activity-of-5b3clq71f5.pdf

Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota

Humans and other mammals are colonized by a vast, complex, and dynamic consortium of microorganisms. One evolutionary driving force for maintaining this metabolically active microbial society is to salvage energy from nutrients, particularly carbohydrates, that are otherwise nondigestible by the host. Much of our understanding of the molecular mechanisms by which members of the intestinal microbiota degrade complex polysaccharides comes from studies of Bacteroides thetaiotaomicron, a prominent and genetically manipulatable component of the normal human and mouse gut. Colonization of germ-free mice with B. thetaiotaomicron has shown how this anaerobe modifies many aspects of intestinal cellular differentiation/gene expression to benefit both host and microbe. These and other studies underscore the importance of understanding precisely how nutrient metabolism serves to establish and sustain symbiotic relationships between mammals and their bacterial partners.

How host-microbial interactions shape the nutrient environment of the mammalian intestine

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics.

/pdf/common-themes-in-microbial-pathogenicity-revisited-5g424sp8ag.pdf

Common themes in microbial pathogenicity revisited.

Uropathogenic strains of Escherichia coli are characterized by the expression of distinctive bacterial properties, products, or structures referred to as virulence factors because they help the organism overcome host defenses and colonize or invade the urinary tract. Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing. This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study. Virulence factor expression is more common among certain genetically related groups of E. coli which constitute virulent clones within the larger E. coli population. In general, the more virulence factors a strain expresses, the more severe an infection it is able to cause. Certain virulence factors specifically favor the development of pyelonephritis, others favor cystitis, and others favor asymptomatic bacteriuria. The currently defined virulence factors clearly contribute to the virulence of wild-type strains but are usually insufficient in themselves to transform an avirulent organism into a pathogen, demonstrating that other as-yet-undefined virulence properties await discovery. Virulence factor testing is a useful epidemiological and research tool but as yet has no defined clinical role. Immunological and biochemical anti-virulence factor interventions are effective in animal models of UTI and hold promise for the prevention of UTI in humans. Images

Virulence factors in Escherichia coli urinary tract infection.

Isolation and phylogenetic analysis of bacteria with antimicrobial activities from the mediterranean sponges aplysina aerophoba and aplysina cavernicola

Temporal variation of the microbial community associated with the mediterranean sponge Aplysina aerophoba

The recent application of molecular microbial ecology tools to sponge-microbe associations has revealed a glimpse into the biodiversity of these microbial communities, that is considered just ‘the tip of the iceberg’. This chapter provides an overview over these new findings with regard to identity, diversity and distribution patterns of sponge-associated microbial consortia. The sponges Aplysina aerophoba (Verongida), Rhopaloeides odorabile (Dicytoceratida) and Theonella swinhoei (Lithistida) were chosen as model systems for this review because they have been subject to both, cultivation-dependent and cultivation-independent approaches. A discussion of the microbial assemblages of Halichondria panicea is presented in the accompanying chapter by Imhoff and Stohr. Considering that a large fraction of sponge-associated microbes is not yet amenable to cultivation, an emphasis has been placed on the techniques centering around the 16S rRNA gene. A section has been included that covers the potential of sponge microbial communities for drug discovery. Finally, a ‘sponge-microbe interaction model’ is presented that summarizes our current understanding of the processes that might have shaped the community structure of the microbial assemblages within sponges.

/pdf/microbial-diversity-of-marine-sponges-3jjmi9ain0.pdf

Microbial diversity of marine sponges.

The uropathogenic Escherichia coli strain J96 (04:K6) is able to produce four adherence factors [P-fimbriae (pap and prs), F1C-fimbriae (foc) and Type 1-fimbriae (fim)], two α-hemolysins (hfyI and II) and the cytotoxic necrotizing factor type 1 (cnf1). Using phenotypic test systems and genotypic analysis, it has been shown that the mutant strain J96-M1 has lost the hlyII, prs and cnf1 genes. The three virulence associated determinants are linked on one particular region on the chromosome, which is termed ‘pathogenicity island II’ (Pai II).

Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and α-hemolysin form the pathogenicity island II of the uropathogenic Escherichia coli strain J96

We have employed electronmicroscopical methods (SEM, TEM) to document the microbial community associated with the marine sponge Aplysina cavernicola (formerly Verongia cavernicola, class Demospongiae). Five dominant bacterial types were identified, three of which resemble the morphotypes originally described by Vacelet (1975). One bacterial type possesses morphological properties that are characteristic of the genus Planctomyces. In addition, morphologically uniform bacteria which reside inside the nuclei of host cells were observed. Using in situ hybridization with fluorescently labelled rRNA probes directed against known bacterial groups, the phylogenetic affiliation of the mesohyl bacteria was assessed. It could be shown that the vast majority of mesohyl bacteria belongs to the domain Bacteria with a low GC content. Among the Bacteria, the delta-Proteobacteria were most abundant, followed by the gamma-Proteobacteria and representatives of the Bacteroides cluster. Clusters of Gram-positive bacteria with a high GC content were also found consistently in low amounts. No hybridization signal was obtained with probes specific to the domain Archaea, to the alpha- and beta-Proteobacteria and to the Cytophaga/Flavobacterium cluster. This study describes for the first time the application of the “top-to-bottom approach” using 16S rRNA probes and in situ hybridization to assess the microbial diversity in Aplysina sponges.

JÃ¶rg Hacker

Papers

Isolation and phylogenetic analysis of bacteria with antimicrobial activities from the mediterranean sponges aplysina aerophoba and aplysina cavernicola

Temporal variation of the microbial community associated with the mediterranean sponge Aplysina aerophoba

Microbial diversity of marine sponges.

Gene clusters encoding the cytotoxic necrotizing factor type 1, Prs-fimbriae and α-hemolysin form the pathogenicity island II of the uropathogenic Escherichia coli strain J96

Microbial diversity in the marine sponge Aplysina cavernicola (formerly Verongia cavernicola) analyzed by fluorescence in situ hybridization (FISH)