72
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities.

          Author Summary

          Many bacterial infections are not the result of colonization and persistence of a single pathogenic microbe in an infection site but instead the result of colonization by several. Although the importance of polymicrobial interactions and pathogenesis has been noted by many prominent microbiologists including Louis Pasteur, most studies of pathogenic microbes have focused on single organism infections. One of the primary reasons for this oversight is the lack of robust model systems for studying bacterial interactions in an infection site. Here, we use a model co-culture system composed of the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans and the common oral commensal Streptococcus gordonii to assess the impact of polymicrobial growth on pathogenesis. We found that the abilities of A. actinomycetemcomitans to persist and cause disease are enhanced during co-culture with S. gordonii. Remarkably, this enhanced persistence requires A. actinomycetemcomitans catabolism of L-lactate, the primary metabolite produced by S. gordonii. These data demonstrate that during co-culture growth, S. gordonii provides a carbon source for A. actinomycetemcomitans that is necessary for establishing a robust polymicrobial infection. This study also demonstrates that virulence of an opportunistic pathogen is impacted by members of the commensal flora.

          Related collections

          Most cited references54

          • Record: found
          • Abstract: found
          • Book: not found

          Bergey's Manual of Determinative Bacteriology

          Based on the data contained in the four-volume Bergey's Manual of Systematic Bacteriology, BMDB-9 also includes new genera and species, new combinations, and new taxa published through the January 1992 issue of the IJSB. Users will find short general descriptions that encompass all organisms by Groups; shape and size, Gram reaction, other pertinent morphological features, motility and flagella, relations to oxygen, basic type of metabolism, carbon and energy sources, habitat and ecology. BMDB-9 also includes discussions of difficulties in identification, keys or tables to genera and species, genus descriptions, synonyms, other nomenclatural changes, and numerous illustrations.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa.

            Certain members of the fluorescent pseudomonads produce and secrete phenazines. These heterocyclic, redox-active compounds are toxic to competing organisms, and the cause of these antibiotic effects has been the focus of intense research efforts. It is largely unknown, however, how pseudomonads themselves respond to - and survive in the presence of - these compounds. Using Pseudomonas aeruginosa DNA microarrays and quantitative RT-PCR, we demonstrate that the phenazine pyocyanin elicits the upregulation of genes/operons that function in transport [such as the resistance-nodulation-cell division (RND) efflux pump MexGHI-OpmD] and possibly in redox control (such as PA2274, a putative flavin-dependant monooxygenase), and downregulates genes involved in ferric iron acquisition. Strikingly, mexGHI-opmD and PA2274 were previously shown to be regulated by the PA14 quorum sensing network that controls the production of virulence factors (including phenazines). Through mutational analysis, we show that pyocyanin is the physiological signal for the upregulation of these quorum sensing-controlled genes during stationary phase and that the response is mediated by the transcription factor SoxR. Our results implicate phenazines as signalling molecules in both P. aeruginosa PA14 and PAO1.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Oral microbial communities in sickness and in health.

              The relationship between humans and their oral microflora begins shortly after birth and lasts a lifetime. Up until fairly recently, the associations between the host and oral bacteria were considered in terms of a multiplicity of single species interactions. However, it is becoming more apparent that the oral microbes comprise a complex community, and that oral health or disease depends on the interface between the host and the microbial community as a whole. Although it is important to continue studies of the pathogenic properties of specific microbes, these are relevant only in the context of the properties of the community within which they reside. Understanding the microbial communities that drive sickness or health is a key to combating human oral diseases.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                1553-7366
                1553-7374
                March 2011
                March 2011
                31 March 2011
                : 7
                : 3
                : e1002012
                Affiliations
                [1 ]Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas, United States of America
                [2 ]Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America
                University of California, San Francisco, United States of America
                Author notes

                Conceived and designed the experiments: MMR KPR MW. Performed the experiments: MMR KPR MW. Analyzed the data: MMR KPR MW. Contributed reagents/materials/analysis tools: MMR KPR MW. Wrote the paper: MMR KPR MW.

                Article
                PPATHOGENS-D-10-00161
                10.1371/journal.ppat.1002012
                3069116
                21483753
                418c9ceb-1531-49d8-ac02-6ffdcd6a7710
                Ramsey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 October 2010
                : 26 January 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Microbiology
                Bacterial Pathogens
                Host-Pathogen Interaction
                Microbial Ecology
                Microbial Metabolism
                Microbial Pathogens
                Microbial Physiology

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article