Abstract
ABSTRACTBacteria rarely inhabit infection sites alone, instead residing in diverse, multispecies communities. Despite this fact, bacterial pathogenesis studies primarily focus on monoculture infections, overlooking how community interactions influence the course of disease. In this study, we used global mutant fitness profiling (transposon sequencing [Tn-seq]) to determine the genetic requirements for the pathogenic bacterium Aggregatibacter actinomycetemcomitans to cause disease when coinfecting with the commensal bacterium Streptococcus gordonii. Our results show that S. gordonii extensively alters A. actinomycetemcomitans requirements for virulence factors and biosynthetic pathways during infection. In addition, we discovered that the presence of S. gordonii enhances the bioavailability of oxygen during infection, allowing A. actinomycetemcomitans to shift from a primarily fermentative to a respiratory metabolism that enhances its growth yields and persistence. Mechanistically, respiratory metabolism enhances the fitness of A. actinomycetemcomitans in vivo by increasing ATP yields via central metabolism and creating a proton motive force. Our results reveal that, similar to cross-feeding, where one species provides another species with a nutrient, commensal bacteria can also provide electron acceptors that promote the respiratory growth and fitness of pathogens in vivo, an interaction that we term cross-respiration.
Highlights
Bacteria rarely inhabit infection sites alone, instead residing in diverse, multispecies communities
Its ability to establish infections likely evolved in the context of other bacterial species that may influence A. actinomycetemcomitans pathogenesis either by promoting or inhibiting its growth within the host
We used sequencing-based mutant fitness profiling (Tn-seq) to globally assess A. actinomycetemcomitans requirements for abscess infection in monoculture and coculture with S. gordonii, a commensal species commonly found with A. actinomycetemcomitans in the oral cavity and abscesses
Summary
Bacteria rarely inhabit infection sites alone, instead residing in diverse, multispecies communities. An emerging paradigm from microbiome studies is that specific community compositions can increase host susceptibility to infection [13, 14] This phenomenon can be partly explained by synergistic interspecies interactions that enhance the virulence of pathogens [15]. While synergistic interactions between microbes clearly impact the fitness of host-associated microbial communities, elucidating the mechanisms controlling synergy within these complex communities has been challenging To tackle this problem, several research groups have taken advantage of simplified (reduced diversity) communities [16,17,18]. Transcriptome sequencing (RNA-seq) examination of monoinfected A. actinomycetemcomitans abscesses revealed that A. actinomycetemcomitans metabolism in vivo is primarily anaerobic [25] These seemingly conflicting observations raise questions about the role of oxygen in A. actinomycetemcomitans-S. gordonii infections. Are oxygen levels constant but high enough to allow A. actinomycetemcomitans L-lactate catabolism/S. gordonii H2O2 production? Or alternatively, are oxygen levels dynamic, increasing in availability during coinfection?
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