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Frank, K. L.

Publications and source records attributed to Frank, K. L..

2 recordsLinked to original sources

Diversity, connectivity and negative interactions define robust microbiome networks across land, stream, and sea

In this era of rapid global change, factors influencing the stability of ecosystems and their functions have come into the spotlight. For decades the relationship between stability and complexity has been investigated in modeled and empirical systems, yet results remain largely context dependent. To overcome this we leverage a multiscale inventory of fungi and bacteria ranging from single sites along an environmental gradient, to habitats inclusive of land, sea and stream, to an entire watershed. We use networks to assess the relationship between microbiome complexity and robustness and identify fundamental principles of stability. We demonstrate that while some facets of complexity are positively associated with robustness, others are not. Beyond positive biodiversity x robustness relationships we find that the number of "gatekeeper" species or those that are highly connected and central within their networks, and the proportion of predicted negative interactions are universal indicators of robust microbiomes. With the potential promise of microbiome engineering to address global challenges ranging from human to ecosystem health we identify properties of microbiomes for future experimental studies that may enhance their stability. We emphasize that features beyond biodiversity and additional characteristics beyond stability such as adaptability should be considered in these efforts.

ecology↗

Manganese acquisition is essential for virulence of Enterococcus faecalis

Manganese (Mn) is an essential micronutrient that is not readily available to pathogens during infection due to an active host defense mechanism known as nutritional immunity. To overcome this nutrient restriction, bacteria utilize high-affinity transporters that allow them to compete with host metal-binding proteins. Despite the established role of Mn in bacterial pathogenesis, little is known about the relevance of Mn in the pathophysiology of E. faecalis. Here, we identified and characterized the major Mn acquisition systems of E. faecalis. We discovered that the ABC-type permease EfaCBA and two Nramp-type transporters, named MntH1 and MntH2, work collectively to promote cell growth under Mn-restricted conditions. The simultaneous inactivation of EfaCBA, MntH1 and MntH2 ({Delta}efa{Delta}mntH1{Delta}mntH2 strain) led to drastic reductions (>95%) in intracellular Mn content, severe growth defects in body fluids (serum and urine) ex vivo, significant loss of virulence in Galleria mellonella, and virtually complete loss of virulence in rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI) models. Despite the functional redundancy of EfaCBA, MntH1 and MntH2 under in vitro or ex vivo conditions and in the invertebrate model, dual inactivation of efaCBA and mntH2 ({Delta}efa{Delta}mntH2 strain) was sufficient to prompt maximal sensitivity to calprotectin, a Mn- and Zn-chelating host antimicrobial protein, and for the loss of virulence in mammalian models. Interestingly, EfaCBA appears to play a prominent role during systemic infection, whereas MntH2 was more important during CAUTI. The different roles of EfaCBA and MntH2 in these sites could be attributed, at least in part, to the differential expression of efaA and mntH2 in cells isolated from hearts or from bladders. Collectively, this study demonstrates that Mn acquisition is essential for the pathogenesis of E. faecalis and validates Mn uptake systems as promising targets for the development of new antimicrobials.

microbiology↗