The constancy of global regulation across a species: the concentrations of ppGpp and RpoS are strain-specific in <it>Escherichia coli</it>

Abstract Background Sigma factors and the alarmone ppGpp control the allocation of RNA polymerase to promoters under stressful conditions. Both ppGpp and the sigma factor σS (RpoS) are potentially subject to variability across the species Escherichia coli. To find out the extent of strain variation we measured the level of RpoS and ppGpp using 31 E. coli strains from the ECOR collection and one reference K-12 strain. Results Nine ECORs had highly deleterious mutations in rpoS, 12 had RpoS protein up to 7-fold above that of the reference strain MG1655 and the remainder had comparable or lower levels. Strain variation was also evident in ppGpp accumulation under carbon starvation and spoT mutations were present in several low-ppGpp strains. Three relationships between RpoS and ppGpp levels were found: isolates with zero RpoS but various ppGpp levels, strains where RpoS levels were proportional to ppGpp and a third unexpected class in which RpoS was present but not proportional to ppGpp concentration. High-RpoS and high-ppGpp strains accumulated rpoS mutations under nutrient limitation, providing a source of polymorphisms. Conclusions The ppGpp and σS variance means that the expression of genes involved in translation, stress and other traits affected by ppGpp and/or RpoS are likely to be strain-specific and suggest that influential components of regulatory networks are frequently reset by microevolution. Different strains of E. coli have different relationships between ppGpp and RpoS levels and only some exhibit a proportionality between increasing ppGpp and RpoS levels as demonstrated for E. coli K-12.</p

The constancy of global regulation across a species: the concentrations of ppGpp and RpoS are strain-specific in Escherichia coli

Abstract Background Sigma factors and the alarmone ppGpp control the allocation of RNA polymerase to promoters under stressful conditions. Both ppGpp and the sigma factor σS (RpoS) are potentially subject to variability across the species Escherichia coli. To find out the extent of strain variation we measured the level of RpoS and ppGpp using 31 E. coli strains from the ECOR collection and one reference K-12 strain. Results Nine ECORs had highly deleterious mutations in rpoS, 12 had RpoS protein up to 7-fold above that of the reference strain MG1655 and the remainder had comparable or lower levels. Strain variation was also evident in ppGpp accumulation under carbon starvation and spoT mutations were present in several low-ppGpp strains. Three relationships between RpoS and ppGpp levels were found: isolates with zero RpoS but various ppGpp levels, strains where RpoS levels were proportional to ppGpp and a third unexpected class in which RpoS was present but not proportional to ppGpp concentration. High-RpoS and high-ppGpp strains accumulated rpoS mutations under nutrient limitation, providing a source of polymorphisms. Conclusions The ppGpp and σS variance means that the expression of genes involved in translation, stress and other traits affected by ppGpp and/or RpoS are likely to be strain-specific and suggest that influential components of regulatory networks are frequently reset by microevolution. Different strains of E. coli have different relationships between ppGpp and RpoS levels and only some exhibit a proportionality between increasing ppGpp and RpoS levels as demonstrated for E. coli K-12

Increased Risk for and Mortality From Invasive Pneumococcal Disease in HIV-Exposed but Uninfected Infants Aged <1 Year in South Africa, 2009–2013

BACKGROUND : High antenatal HIV seroprevalence rates (∽30%) with low perinatal HIV transmission rates (2.5%) due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed-uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants. METHODS : We conducted a cross-sectional study of infants aged <1 year with IPD enrolled in a national, laboratory-based surveillance program for incidence estimations. Incidence was reported for two time points, 2009 and 2013. At enhanced sites we collected additional data including HIV status and in-hospital outcome. RESULTS : We identified 2099 IPD cases in infants from 2009-2013 from all sites. In infants from enhanced sites (n=1015), 92% had known HIV exposure status and 86% had known outcomes. IPD incidence was highest in HIV-infected infants, ranging from 272-654/100,000 population between time points (2013 and 2009), followed by HEU (33-88/100,000) and HIV-unexposed-uninfected (HUU) infants (18-28/100,000). Case fatality rate in HEU (29%, 74/253) was intermediate between HUU (25%, 94/377) and HIV-infected infants (34%, 81/242). When restricted to cases <6 months of age, HEU infants (37%, 59/175) were at significantly higher risk of dying than HUU infants (32%, 51/228; Adjusted relative risk ratio = 1.76 [95% confidence interval 1.09-2.85]). DISCUSSION : HEU infants are at increased risk of IPD and mortality from IPD compared with HUU children, especially as young infants. HEU infants, whose numbers will likely continue to increase, should be prioritized for interventions such as pneumococcal vaccination along with HIV-infected infants and children.http://cid.oxfordjournals.org2016-05-31hb201

Correction to: An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids (Genetics in Medicine, (2021), 23, 4, (740-750), 10.1038/s41436-020-01027-3)

In the original author list, Seth Perlman’s degrees were listed as MD, PhD. Dr Perlman’s degree is MD. The original version has been corrected