Abstract
A number of human infections are characterized by the presence of more than one bacterial species and are defined as polymicrobial diseases. Methods for the analysis of the complex biological interactions in mixed infections with a large number of microorganisms are limited and do not effectively determine the contribution of each bacterial species to the pathogenesis of the polymicrobial community. We have developed a novel Drosophila melanogaster infection model to study microbe–microbe interactions and polymicrobe–host interactions. Using this infection model, we examined the interaction of 40 oropharyngeal isolates with Pseudomonas aeruginosa. We observe three classes of microorganisms, one of which acts synergistically with the principal pathogen, while being avirulent or even beneficial on its own. This synergy involves microbe–microbe interactions that result in the modulation of P. aeruginosa virulence factor gene expression within infected Drosophila. The host innate immune response to these natural-route polymicrobial infections is complex and characterized by additive, suppressive, and synergistic transcriptional activation of antimicrobial peptide genes. The polymicrobial infection model was used to differentiate the bacterial flora in cystic fibrosis (CF) sputum, revealing that a large proportion of the organisms in CF airways has the ability to influence the outcome of an infection when in combination with the principal CF pathogen P. aeruginosa.
Highlights
IntroductionSuitable models are required to study the microbe– microbe interactions within these mixed infections, as well as the complex interplay between the polymicrobial communities and the host immune system [1]
Infections marked with more than one bacterial species are common
We previously showed that Viridans group streptococci and coagulasenegative staphylococci represent noteworthy classes of oropharyngeal flora (OF) due to their capacity to modulate the gene expression of the principal pathogen Pseudomonas aeruginosa, which results in enhanced expression of many important virulence factors
Summary
Suitable models are required to study the microbe– microbe interactions within these mixed infections, as well as the complex interplay between the polymicrobial communities and the host immune system [1]. Results from both molecular typing and microbiologic techniques on endobrochial secretions have defined cystic fibrosis (CF) lower airway disease with polymicrobial etiology [2,3,4,5,6,7,8]. In patients with CF, defective mucocilliary clearance [9] and impaired innate immunity [10], lead to chronic pulmonary infections These are characterized by long periods of stability (despite high bacterial loads) that are punctuated by episodes of overt immunologic responses that cause the majority of irreversible lung damage. The complexity of polymicrobial infections, such as those in CF, make them difficult to study and there are practical limits to the use of mammalian models for an adequate dissection of the multifarious biological interactions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
