Biomimetic Materials to Characterize Bacteria-host Interactions

et al. 2015

Molecular Microbiology

SummaryShigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S. sonnei adhesin, SSO1327 which is a multivalent adhesion molecule (MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S. sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is nonredundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsAdependent and independent attachment and invasion by deoxycholate in Shigella flexneri, deoxycholate negatively regulates IcsA and MAM in S. sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response.

Section: Methodsmentioning

confidence: 97%

The Multivalent Adhesion Molecule SSO1327 plays a key role in Shigella sonnei pathogenesis

Mahmoud

et al. 2015

Molecular Microbiology

“…Purified GST-MAM7ΔN44 or GST alone were chemically coupled to polystyrene microbeads, as previously described31, to produce inhibitor and control beads, respectively.…”

Section: Methodsmentioning

confidence: 99%

Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury

Huebinger

Santos

et al. 2016

Sci Rep

Self Cite

Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence. Thus, targeting MAM-based adherence is a promising strategy for displacing pathogens from host tissues and inhibiting infection. Here, we show that topical application of polymeric microbeads functionalized with the adhesin MAM7 to a burn infected with multidrug-resistant Pseudomonas aeruginosa substantially decreased bacterial loads in the wound and prevented the spread of the infection into adjacent tissues. As a consequence, the application of this adhesion inhibitor allowed for vascularization and wound healing, and maintained local and systemic inflammatory responses to the burn. We propose that MAM7-functionalized microbeads can be used as a topical treatment, to reduce bacterial attachment and hence prevent bacterial colonization and infection of wounds. As adhesion is not required for microbial survival, this anti-infective strategy has the potential to treat multidrug-resistant infections and limit the emergence of drug-resistant pathogens.

“…Since adhesion and effects on host signaling are so interlinked, these two activities have been difficult to dissect genetically, using a reductionist approach — deletion of adhesins often impacts effector function by abrogating translocation efficiency. Rather, a minimalistic approach, studying adhesion and resulting signaling using either nonadhesive heterologous strains expressing adhesins [55], or purified adhesins reconstituted on a surface that geometrically resembles bacteria, has facilitated the analysis of effector activities mediated by adhesins [56]. The following are some examples to demonstrate the breadth of interactions and signaling pathways co-opted by adhesins.…”

Section: Introductionmentioning

confidence: 99%

Against the tide: the role of bacterial adhesion in host colonization

Biochemical Society Transactions

Krachler

2016

Evolving under the constant exposure to an abundance of diverse microbial life, the human body has developed many ways of defining the boundaries between self and non-self. Many physical and immunological barriers to microbial invasion exist, and yet bacteria have found a multitude of ways to overcome these, initiate interactions with and colonize the human host. Adhesion to host cells and tissues is a key feature allowing bacteria to persist in an environment under constant flux and to initiate transient or permanent symbioses with the host. This review discusses reasons why adhesion is such a seemingly indispensable requirement for bacteria–host interactions, and whether bacteria can bypass the need to adhere and still persist. It further outlines open questions about the role of adhesion in bacterial colonization and persistence within the host.