Staphylococcus aureus has recently overtaken Pseudomonas aeruginosa as the most commonly recognized bacterial pathogen that infects the respiratory tracts of individuals with the genetic disease cystic fibrosis (CF) in the United States. Most studies of S. aureus in CF patient lung infections have focused on a few isolates, often exclusively laboratory-adapted strains, and how they are killed by P. aeruginosa. Less is known about the diversity of S. aureus CF patient lung isolates in terms of both their virulence and their interaction with P. aeruginosa. To begin to address this gap, we recently sequenced 64 clinical S. aureus isolates and a reference isolate, JE2. Here, we analyzed the antibiotic resistance genotypes, sequence types, clonal complexes, spa types, agr types, and presence/absence of other known virulence factor genes of these isolates. We hypothesized that virulence phenotypes of S. aureus, namely, toxin production and the mucoid phenotype, would be lost in these isolates due to adaptation in the CF patient lung. In contrast to these expectations, we found that most isolates can lyse both rabbit and sheep blood (67.7%) and produce polysaccharide (69.2%), suggesting that these phenotypes were not lost during adaptation to the CF lung. We also identified three distinct phenotypic groups of S. aureus based on their survival in the presence of nonmucoid P. aeruginosa laboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity of S. aureus isolates from CF patients, specifically the distribution of important virulence factors and their interaction with P. aeruginosa, all of which have implications in patient health. IMPORTANCE Staphylococcus aureus is now the most frequently detected recognized pathogen in the lungs of individuals who have cystic fibrosis (CF) in the United States, followed closely by Pseudomonas aeruginosa. When these pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. While P. aeruginosa has been rigorously studied in the context of bacterial pathogenesis in CF, less is known about S. aureus. Here, we present an in-depth study of 64 S. aureus clinical isolates from CF patients, for which we investigated genetic diversity utilizing whole-genome sequencing, virulence phenotypes, and interactions with P. aeruginosa. We found that S. aureus isolated from CF lungs are phylogenetically diverse; most retain known virulence factors and vary in their interactions with P. aeruginosa (i.e., they range from being highly sensitive to P. aeruginosa to completely tolerant to it). Deepening our understanding of how S. aureus responds to its environment and other microbes in the CF lung will enable future development of effective treatments and preventative measures against these formidable infections.
Staphylococcus aureus is a globally pervasive pathogen that produces a plethora of toxic molecules that can harm host immune cells. Production of these toxins is mainly controlled by an active agr quorum-sensing system, which senses and responds to bacterial cell density.
The productivity of a biological community often correlates with its diversity. In the microbial world this phenomenon can sometimes be explained by positive, density-dependent interactions such as cross-feeding and syntrophy. These metabolic interactions help account for the astonishing variety of microbial life and drive many of the biogeochemical cycles without which life as we know it could not exist. While it is difficult to recapitulate experimentally how these interactions evolved among multiple taxa, we can explore in the laboratory how they arise within one. These experiments provide insight into how different bacterial ecotypes evolve and from these, possibly new “species.” We have previously shown that in a simple, constant environment a single clone of Escherichia coli can give rise to a consortium of genetically and phenotypically differentiated strains, in effect, a set of ecotypes, that coexist by cross-feeding. We marked these different ecotypes and their shared ancestor by integrating fluorescent protein into their genomes and then used flow cytometry to show that each evolved strain is more fit than the shared ancestor, that pairs of evolved strains are fitter still, and that the entire consortium is the fittest of all. We further demonstrate that the rank order of fitness values agrees with estimates of yield, indicating that an experimentally evolved consortium more efficiently converts primary and secondary resources to offspring than its ancestor or any member acting in isolation. IMPORTANCE Polymicrobial consortia occur in both environmental and clinical settings. In many cases, diversity and productivity correlate in these consortia, especially when sustained by positive, density-dependent interactions. However, the evolutionary history of such entities is typically obscure, making it difficult to establish the relative fitness of consortium partners and to use those data to illuminate the diversity-productivity relationship. Here, we dissect an Escherichia coli consortium that evolved under continuous glucose limitation in the laboratory from a single common ancestor. We show that a partnership consisting of cross-feeding ecotypes is better able to secure primary and secondary resources and to convert those resources to offspring than the ancestral clone. Such interactions may be a prelude to a special form of syntrophy and are likely determinants of microbial community structure in nature, including those having clinical significance such as chronic infections.
26Community productivity often correlates with diversity. In the microbial world this phenomenon 27 can sometimes be explained by highly-specific metabolic interactions that include cross-feeding 28 and syntrophy. Such interactions help account for the astonishing variety of microbial life, and 29 drive many of the biogeochemical cycles without which life as we know it could not exist. While 30 it is difficult to recapitulate experimentally how these interactions evolved among multiple taxa, 31 we can explore in the laboratory how they arise within one. These experiments provide insight into 32 how different bacterial ecotypes evolve and from these, possibly new 'species. ' We have 33 previously shown that in a simple, constant environment a single clone of E. coli can give rise to 34 a consortium of genetically-and physiologically-differentiated strains, in effect, a set of ecotypes, 35 that coexist by cross-feeding. We marked these different ecotypes and their shared ancestor by 36 integrating fluorescent protein into their genomes. We then used flow cytometry to show that each 37 strain by itself is more fit than the shared ancestor, that pairs of evolved strains are fitter still, and 38 that the entire consortium is fittest of all. We further demonstrate that the rank order of fitness 39 values agrees with estimates of yield, indicating that an experimentally evolved consortium more 40 efficiently converts resources to offspring than its ancestor or any member acting in isolation. 41 42 Importance: In the microbial world, diversity and productivity of communities and consortia 43 often correlate positively. However, it is challenging to tease apart a consortium whose members 44 have co-evolved, and connect estimates of their fitness and the fitness of their ancestor(s) with 45 estimates of productivity. Such analyses are prerequisite to understanding the evolutionary origins 46 4 of all biological communities. Here we dissect an E. coli consortium that evolved in the laboratory 47 and show that cooperative interactions are favored under continuous glucose limitation because a 48 partnership of ecotypes is better able to scavenge all available resources and more efficiently 49 convert those resources to offspring than any single individual. Such interactions may be a prelude 50 to a special form of syntrophy, and are likely to be key determinants of microbial community 51 structure in nature, including those having clinical significance, such as chronic infections. 52 53 Microbial communities in nature exhibit enormous genetic diversity owing in part to the 54 extreme spatial and temporal heterogeneity of life at the micron scale. This heterogeneity opens 55 up ample opportunities for selection and drift to act differentially on new variants arising by 56 mutation, horizontal gene transfer or arriving via dispersal. Over geologic time-scales these 57 evolutionary forces have enabled microbes to exploit almost every conceivable environment on 58 and in the earth's crust, where they partition niches...
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