Proteomic profiling of the carbon-starved Escherichia coli reveals upregulation of stress-inducible pathways implicated in biological adhesion and methylglyoxal metabolism.

Starvation in bacteria is a complex adaptive response to deprivation of nutrients that has been shown to implicate a number of stress networks that modulate pathogenicity and antibiotic resistance. Starvation in nature is qualitatively different from in-culture late stationary phase energy source depletion. To look into proteome-level alterations elicited by complete elimination of carbon source, we used Escherichia coli HT115-derived SLE1 strain cells and a combination of label-free and metabolic isotope labeling approaches. We isolated pathways differentially affected by carbon starvation and observed robust upregulation of proteins implicated in networks belonging to Gene Ontology terms 'Biological adhesion' and 'Methylglyoxal metabolic process'.

The prevalence of Borrelia in Ixodes persulcatus in southeastern Kazakhstan.

Borreliosis is one of the most common vector-borne zoonotic diseases in the world. Limited data are available regarding Borrelia spp. and their genotypes in Kazakhstan. The goal of this study was to investigate the prevalence of Borrelia spp. in ixodid ticks collected in the southeastern region of Kazakhstan. A total of 1907 ixodid ticks were collected by flagging vegetation at three collection areas in the Almaty oblast between 2015 and 2018. They were grouped into 407 pools and examined by qPCR for Borrelia burgdorferi sensu lato (s.l.). A conventional PCR with specific primers targeting 16S rRNA gene was used to differentiate B. burgdorferi s.l. genospecies. Sequence analysis of the PCR products was performed for sixteen samples. Lyme borreliosis agents were only detected in adult questing Ixodes persulcatus. The overall B. burgdorferi s.l. prevalence in I. persulcatus estimated as the minimum infection rate reached 10.7 %. Borrelia burgdorferi sensu stricto was not detected in any of the tick pools. Partial 16S rRNA gene sequencing revealed the presence of B. miyamotoi, B. afzelii, and B. garinii. Borrelia afzelii was the dominant genospecies in Almaty oblast. A significantly lower proportion of B. garinii positive tick pools was detected in the Zailiyskiy Alatau as compared to the Dzungarian Alatau (χ2 = 16.243; p = 0.0001) and Yenbekshikazakh district (χ2 = 7.4156; p = 0.0065). The obtained results indicate the epidemiological significance of B. afzelii and B. garinii in southeastern Kazakhstan. These new data aim to improve the diagnostics of Lyme borreliosis and monitoring of tick-borne infections in Kazakhstan.

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis).

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed.

ER stress inhibits mTORC2 and Akt signaling through GSK-3ß-mediated phosphorylation of rictor.

In response to environmental cues, cells coordinate a balance between anabolic and catabolic pathways. In eukaryotes, growth factors promote anabolic processes and stimulate cell growth, proliferation, and survival through activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. Akt-mediated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) inhibits its enzymatic activity, thereby stimulating glycogen synthesis. We show that GSK-3ß itself inhibits Akt by controlling the mammalian target of rapamycin complex 2 (mTORC2), a key activating kinase for Akt. We found that during cellular stress, GSK-3ß phosphorylated the mTORC2 component rictor at serine-1235, a modification that interfered with the binding of Akt to mTORC2. The inhibitory effect of GSK-3ß on mTORC2-Akt signaling and cell proliferation was eliminated by blocking phosphorylation of rictor at serine-1235. Thus, in response to cellular stress, GSK-3ß restrains mTORC2-Akt signaling by specifically phosphorylating rictor, thereby balancing the activities of GSK-3ß and Akt, two opposing players in glucose metabolism.