title: Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism.
abstract: Pathogen attachment to host cells is a key process during infection, and inhibition of pathogen adhesion is a promising approach to the prevention of infectious disease. We have previously shown that multivalent adhesion molecules (MAMs) are abundant in both pathogenic and commensal bacterial species, mediate early attachment to host cells, and can contribute to virulence. Here, we investigated the efficacy of an engineered bacterium expressing a commensal MAM on its surface in preventing pathogen attachment and pathogen-mediated cytotoxicity in a tissue culture infection model. We were able to dissect the individual contributions of adhesion and interspecific antagonism on the overall outcome of infection for a range of different pathogens by comparison with the results obtained with a fully synthetic adhesion inhibitor. We found that the potential of the engineered bacterium to outcompete the pathogen is not always solely dependent on its ability to hinder host attachment but, depending on the pathogenic species, may also include elements of interspecific antagonism, such as competition for nutrients and its ability to cause a loss of fitness due to production of antimicrobial factors.
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Fitua
authors.initials: F
authors.lastname: Al-Saedi
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Daniel Henry
authors.initials: DH
authors.lastname: Stones
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Diana Pereira
authors.initials: DP
authors.lastname: Vaz
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom a.krachler@bham.ac.uk.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Krachler
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D000898:Antibiosis; D001422:Bacterial Adhesion; D060846:Cell Engineering; D013293:Enterococcus faecalis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015870:Gene Expression; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D011993:Recombinant Fusion Proteins