A heritable iron memory enables decision-making in Escherichia coli.

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This "iron" memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with its iron memory, is passed down to its fourth-generation daughter cells. This memory is naturally lost by the seventh generation, but artificially manipulating iron levels allows it to persist much longer. A mathematical model with a time-delay component faithfully recreates the observed dynamic interconversions between different swarming potentials. We demonstrate that cellular iron levels also track with biofilm formation and antibiotic tolerance, suggesting that iron memory may impact other physiologies.

Cellular Mn/Zn Ratio Influences Phosphoglucomutase Activity and Capsule Production in Streptococcus pneumoniae D39.

Capsular polysaccharide (CPS) is a major virulence determinant for many human-pathogenic bacteria. Although the essential functional roles for CPS in bacterial virulence have been established, knowledge of how CPS production is regulated remains limited. Streptococcus pneumoniae (pneumococcus) CPS expression levels and overall thickness change in response to available oxygen and carbohydrate. These nutrients in addition to transition metal ions can vary significantly between host environmental niches and infection stage. Since the pneumococcus must modulate CPS expression among various host niches during disease progression, we examined the impact of the nutritional transition metal availability of manganese (Mn) and zinc (Zn) on CPS production. We demonstrate that increased Mn/Zn ratios increase CPS production via Mn-dependent activation of the phosphoglucomutase Pgm, an enzyme that functions at the branch point between glycolysis and the CPS biosynthetic pathway in a transcription-independent manner. Furthermore, we find that the downstream CPS protein CpsB, an Mn-dependent phosphatase, does not promote aberrant dephosphorylation of its target capsule-tyrosine kinase CpsD during Mn stress. Together, these data reveal a direct role for cellular Mn/Zn ratios in the regulation of CPS biosynthesis via the direct activation of Pgm. We propose a multilayer mechanism used by the pneumococcus in regulating CPS levels across various host niches. IMPORTANCE Evolving evidence strongly indicates that maintenance of metal homeostasis is essential for establishing colonization and continued growth of bacterial pathogens in the vertebrate host. In this study, we demonstrate the impact of cellular manganese/zinc (Mn/Zn) ratios on bacterial capsular polysaccharide (CPS) production, an important virulence determinant of many human-pathogenic bacteria, including Streptococcus pneumoniae. We show that higher Mn/Zn ratios increase CPS production via the Mn-dependent activation of the phosphoglucomutase Pgm, an enzyme that functions at the branch point between glycolysis and the CPS biosynthetic pathway. The findings provide a direct role for Mn/Zn homeostasis in the regulation of CPS expression levels and further support the ability of metal cations to act as important cellular signaling mediators in bacteria.

Methane emissions respond to soil temperature in convergent patterns but divergent sensitivities across wetlands along altitude.

Among the global coordinated patterns in soil temperature and methane emission from wetlands, a declining trend of optimal soil temperature for methane emissions from low to high latitudes has been witnessed, while the corresponding trend along the altitudinal gradient has not yet been investigated. We therefore selected two natural wetlands located at contrasting climatic zones from foothill and mountainside of Nepal Himalayas, to test: (1) whether the optimal temperature for methane emissions decreases from low to high altitude, and (2) whether there is a difference in temperature sensitivity of methane emissions from those wetlands. We found significant spatial and temporal variation of methane emissions between the two wetlands and seasons. Soil temperature was the dominant driver for seasonal variation in methane emissions from both wetlands, though its effect was perplexed by the level of standing water, aquatic plants, and dissolved organic carbon, particularly in the deep water area. When integrative comparison was conducted by adding the existing data from wetlands of diverse altitudes, and the latitude-for-altitude effect was taken into account, we found the baseline soil temperatures decrease whilst the altitude rises with respect to a rapid increase in methane emission from all wetlands, however, remarkably higher sensitivity of methane emissions to soil temperature (apparent Q10 ) was found in mid-altitude wetland. We provide the first evidence of an apparent decline in optimal temperature for methane emissions with increasing elevation. These findings suggest a convergent pattern of methane emissions with respect to seasonal temperature shifts from wetlands along altitudinal gradient, while a divergent pattern in temperature sensitivities exhibits a single peak in mid-altitude.

A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus.

Maintaining manganese (Mn) homeostasis is important for the virulence of numerous bacteria. In the human respiratory pathogen Streptococcus pneumoniae, the Mn-specific importer PsaBCA, exporter MntE, and transcriptional regulator PsaR establish Mn homeostasis. In other bacteria, Mn homeostasis is controlled by yybP-ykoY family riboswitches. Here, we characterize a yybP-ykoY family riboswitch upstream of the mgtA gene encoding a PII-type ATPase in S. pneumoniae, suggested previously to function in Ca2+ efflux. We show that the mgtA riboswitch aptamer domain adopts a canonical yybP-ykoY structure containing a three-way junction that is compacted in the presence of Ca2+ or Mn2+ at a physiological Mg2+ concentration. Although Ca2+ binds to the RNA aptamer with higher affinity than Mn2+, in vitro activation of transcription read-through of mgtA by Mn2+ is much greater than by Ca2+. Consistent with this result, mgtA mRNA and protein levels increase ≈5-fold during cellular Mn stress, but only in genetic backgrounds of S. pneumoniae and Bacillus subtilis that exhibit Mn2+ sensitivity, revealing that this riboswitch functions as a failsafe 'on' signal to prevent Mn2+ toxicity in the presence of high cellular Mn2+. In addition, our results suggest that the S. pneumoniae yybP-ykoY riboswitch functions to regulate Ca2+ efflux under these conditions.

Prolonged use of noninvasive ventilation in the management of COVID-19-induced ARDS: a case report.

The severity of coronavirus disease 2019 and its manifestations varies considerably from person to person. Acute respiratory distress syndrome is the more feared and severe complication usually managed with early intubation and invasive ventilation. We report a case from a tertiary hospital in Nepal admitted with coronavirus disease 2019 acute respiratory distress syndrome and managed primarily on noninvasive ventilation. Considering the scarcity of invasive ventilation and the rising number of cases during the pandemic and its complications, early use of noninvasive ventilation in appropriate patients can decrease the need for invasive ventilation.

Iron Memory in E. coli.

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when E. coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This memory pre-exists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, whether low or high, is passed down to its fourth-generation daughter cells. This memory is naturally lost by the seventh generation, but artificially manipulating iron levels allows it to persist much longer. A mathematical model with a time-delay component faithfully recreates the observed dynamic interconversions between different swarming potentials. We also demonstrate that iron memory can integrate multiple stimuli, impacting other bacterial behaviors such as biofilm formation and antibiotic tolerance.

Diagnosis and management of hepatolithiasis in an adult patient: A case report.

Hepatolithiasis or intrahepatic calculi are common in South East Asia but are rare in Western nations. The primary symptom of the condition is recurrent pain in the upper abdomen. Stones in the cystic duct or common bile duct are also common findings. Recurrent pyogenic cholangitis is the most frequent complication. Radiological studies and percutaneous procedures are vital for diagnosing and managing this condition. The primary goal in treating the condition is to decrease the chance of developing cholangitis and to stop the progression of the disease, which may lead to biliary cirrhosis.