More than 10% of the global human population is now afflicted with kidney stones, which are commonly associated with other significant health problems including diabetes, hypertension and obesity. Nearly 70% of these stones are primarily composed of calcium oxalate, a mineral previously assumed to be effectively insoluble within the kidney. This has limited currently available treatment options to painful passage and/or invasive surgical procedures. We analyze kidney stone thin sections with a combination of optical techniques, which include bright field, polarization, confocal and super-resolution nanometer-scale auto-fluorescence microscopy. Here we demonstrate using interdisciplinary geology and biology (geobiology) approaches that calcium oxalate stones undergo multiple events of dissolution as they crystallize and grow within the kidney. These observations open a fundamentally new paradigm for clinical approaches that include in vivo stone dissolution and identify high-frequency layering of organic matter and minerals as a template for biomineralization in natural and engineered settings.
A microfluidic
gradient chamber (MGC) and a homogeneous batch culturing
system were used to evaluate whether spatial concentration gradients
of the antibiotic ciprofloxacin allow development of greater antibiotic
resistance in Escherichia coli strain
307 (E. coli 307) compared to exclusively
temporal concentration gradients, as indicated in an earlier study.
A linear spatial gradient of ciprofloxacin and Luria–Bertani
broth (LB) medium was established and maintained by diffusion over
5 days across a well array in the MGC, with relative concentrations
along the gradient of 1.7–7.7× the original minimum inhibitory
concentration (MICoriginal). The E. coli biomass increased in wells with lower ciprofloxacin concentrations,
and only a low level of resistance to ciprofloxacin was detected in
the recovered cells (∼2× MICoriginal). Homogeneous
batch culture experiments were performed with the same temporal exposure
history to ciprofloxacin concentration, the same and higher initial
cell densities, and the same and higher nutrient (i.e., LB) concentrations
as in the MGC. In all batch experiments, E. coli 307 developed higher ciprofloxacin resistance after exposure, ranging
from 4 to 24× MICoriginal in all replicates. Hence,
these results suggest that the presence of spatial gradients appears
to reduce the driving force for E. coli 307 adaptation to ciprofloxacin, which suggests that results from
batch experiments may over predict the development of antibiotic resistance
in natural environments.
We fabricated a microfluidic reactor
with a nanoporous barrier
to characterize electron transport between Shewanella
oneidensis MR-1 and the metal oxide birnessite across
a physical separation. Real-time quantification of electron flux across
this barrier by strains with different electron transfer capabilities
revealed that this bacterium exports flavins to its surroundings when
faced with no direct physical access to an electron acceptor, allowing
it to reduce metals at distances exceeding 60 μm. An energy
balance indicates that flavins must be recycled for S. oneidensis MR-1 to yield energy from lactate oxidation
coupled to flavin reduction. In our system, we find that flavins are
recycled between 24 and 60 times depending on flow conditions. This
energy saving strategy, which until now had not been systematically
tested or captured in environmentally relevant systems, suggests that
electron shuttling microorganisms have the capacity to access and
reduce metals in physically distant or potentially toxic microenvironments
(i.e., pores with soluble and transiently sorbed toxins) where direct
contact is limited or unfavorable. Our results challenge the prediction
that diffusion-based electron shuttling is only effective across short
distances and may lead to improved bioremediation strategies or advance
biogeochemical models of electron transfer in anaerobic sediments.
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