Cytokine Storm: A Suicidal Immune Response to Novel Corona Virus

SARS-CoV-2 virus is responsible for the COVID-19 disease in patients. Only 15-20 % of COVID-19 patients have developed severe pulmonary symptoms and illness, which are fatal to patients. Hyper-immune response to the SARS-CoV-2 virus by the host’s immune system causes the release and over production of certain kinds of inflammatory mediators and cytokines. And it results in the cytokine storm. Cytokine storm produces the hyper inflammatory reaction, which deteriorates the cells and tissue. This type of immune response is host killing and suicidal response to the SARS-CoV-2 virus by the host. This suicidal response ultimately leads to lung damage, respiratory tract pneumonia, ARDS, multi-organ failure at a later stage and ultimately death. Hence, it needs to suppress the hyper-functioning of the immune system to inhibit the cytokine release and cytokine storm. Anti-inflammatory and immuno-modulatory drugs can be repurposed to manage the cytokine storm and hyper-immune response. Inhibition and management of the host’s suicidal immune response and cytokine storm, could be life-saving and reduce the mortality rate in COVID-19 patients.

Wine Phenolic Compounds Differently Affect the Host-Killing Activity of Two Lytic Bacteriophages Infecting the Lactic Acid Bacterium Oenococcus oeni

To provide insights into phage-host interactions during winemaking, we assessed whether phenolic compounds modulate the phage predation of Oenococcus oeni. Centrifugal partition chromatography was used to fractionate the phenolic compounds of a model red wine. The ability of lytic oenophage OE33PA to kill its host was reduced in the presence of two collected fractions in which we identified five compounds. Three, namely, quercetin, myricetin and p-coumaric acid, significantly reduced the phage predation of O. oeni when provided as individual pure molecules, as also did other structurally related compounds such as cinnamic acid. Their presence was correlated with a reduced adsorption rate of phage OE33PA on its host. Strikingly, none of the identified compounds affected the killing activity of the distantly related lytic phage Vinitor162. OE33PA and Vinitor162 were shown to exhibit different entry mechanisms to penetrate into bacterial cells. We propose that ligand-receptor interactions that mediate phage adsorption to the cell surface are diverse in O. oeni and are subject to differential interference by phenolic compounds. Their presence did not induce any modifications in the cell surface as visualized by TEM. Interestingly, docking analyses suggest that quercetin and cinnamic acid may interact with the tail of OE33PA and compete with host recognition.

Evolution of increased virulence is associated with decreased spite in the insect-pathogenic bacterium Xenorhabdus nematophila

Disease virulence may be strongly influenced by social interactions among pathogens, both during the time course of an infection and evolutionarily. Here, we examine how spiteful bacteriocin production in the insect-pathogenic bacterium Xenorhabdus nematophila is evolutionarily linked to its virulence. We expected a negative correlation between virulence and spite owing to their inverse correlations with growth. We examined bacteriocin production and growth across 14 experimentally evolved lineages that show faster host-killing relative to their ancestral population. Consistent with expectations, these more virulent lineages showed reduced bacteriocin production and faster growth relative to the ancestor. Further, bacteriocin production was negatively correlated with growth across the examined lineages. These results strongly support an evolutionary trade-off between virulence and bacteriocin production and lend credence to the view that disease management can be improved by exploiting pathogen social interactions.

Factors affecting the biology of Pachycrepoideus vindemmiae (Hymenoptera: Pteromalidae) on spotted-wing drosophila (Drosophila suzukii)

Pachycrepoideus vindemmiae is a parasitoid of the invasive spotted-wing drosophila (SWD, Drosophila suzukii) in the U.S. Few studies have addressed interactions between these two species and little is known about the potential of this parasitoid as a biocontrol agent of SWD. Here, we investigated the impact of extrinsic and intrinsic factors on life-history traits of P. vindemmiae. Both constant (entire adulthood) and limited (30 minutes) supply of water + honey, honey, or host increased parasitoid survival compared to controls (water or fasting). Water + honey caused the highest parasitoid survivals (35-60 days), independent of supply period, sex, and host availability. Females were intrinsically more resistant to water and honey scarcity than males, and host-feeding elevated such resistance even higher. Constant supply of honey supported the highest host-killing capacity (ca. 600 SWD pupae/wasp). However, in young females (4-9 days old), such honey effect was insignificant while water deprivation (either with or without honey) resulted in the highest host-killing potential. This indicate that although sugar becomes a critical nutritional resource as females age, young females depend more on water than sugar. No effect of water nor honey was observed on the sex ratio of young females, but when we considered the entire adulthood honey supply produced the lowest proportion of females (0.50), independent of water availability. Such reduction derived from sperm depletion, likely caused by both lack of re-mating and higher fecundity in honey-fed wasps. Neither water nor honey affected parasitoid emergence rate (0.97), independent of female age. Based on survival and host-killing capacity, we conclude that P. vindemmiae has a tremendous biocontrol potential against SWD. Both limited and constant supply of water, sugar, and host increase parasitoid survival, while constant supply of water and/or honey enhance its host-killing potential and decrease sex ratio depending on mother age.

From unique killers to a jumbo genome - isolation and characterization of phages that infect the plant pathogen, Agrobacterium tumefaciens

Bacteriophages and their lytic peptides can protect plants from phytopathogens such as Agrobacterium tumefaciens. To better understand mechanisms of phagemediated host killing, we isolated and characterized five lytic bacteriophages with activity against A. tumefaciens C58. These phages come in different shapes and sizes--from T7-like phages with podoviral morphology and isometric heads to T4-like phages with myoviral morphology and a contractile tail--and exhibit varying host ranges and killing efficiencies. The smallest Agrobacterium phages are phiKMVlike phages in the T7 superfamily that are efficient at killing their hosts. Their lethality can be attributed to their expression of a unique endolysin, called Phage Peptidoglycan Hydrolase (PPH). The atypical domain structure of PPH, along with the absence of obvious accessory proteins, suggest PPH may function independently to mediate host cell lysis. Contrary to the narrow host range of the phage, expression of PPH from an inducible promoter inhibits cell growth and blocks cell division in a broad range of bacteria including Agrobacterium, Sinorhizobium, and Escherichia strains. Another member of the Podoviridae family, Atu_ph08, carries remnants of a lysogen and shares 60.2% identity with Agrobacterium genomospecies 3. The T4-like phages in our collection are not potent killers. Atu_ph04 is unique T4-like phage that is similar to a group of rhizophages. The largest Agrobacterium phage, Atu_ph07, has a head diameter of 146 nm, an extended tail length of 136 nm, and a genome of 490 kbp. Our results indicate a high degree of morphological and genomic diversity and also suggest novel mechanisms of host cell killing remain to be uncovered.

An engineered bacterium auxotrophic for an unnatural amino acid: a novel biological containment system

Biological containment is a genetic technique to program dangerous organisms to grow only in the laboratory and to die in the natural environment. Auxotropy for a substance not found in the natural environment is an ideal biological containment. Here, we constructed an Escherichia coli strain that cannot survive in the absence of the unnatural amino acid 3-iodo-L-tyrosine. This synthetic auxotrophy was achieved by conditional production of the antidote protein against the highly toxic enzyme colicin E3. An amber stop codon was inserted in the antidote gene. The translation of the antidote mRNA was controlled by a translational switch using amber-specific 3-iodo-L-tyrosine incorporation. The antidote is synthesized only when 3-iodo-L-tyrosine is present in the culture medium. The viability of this strain rapidly decreased with less than a 1 h half-life after removal of 3-iodo-L-tyrosine, suggesting that the decay of the antidote causes the host killing by activated colicin E3 in the absence of this unnatural amino acid. This containment system can be constructed by only plasmid introduction without genome editing, suggesting that this system may be applicable to other microbes carrying toxin-antidote systems similar to that of colicin E3.

An engineered bacterium auxotrophic for an unnatural amino acid: a novel biological containment system

Biological containment is a genetic technique to program dangerous organisms to grow only in the laboratory and to die in the natural environment. Auxotropy for a substance not found in the natural environment is an ideal biological containment. Here, we constructed an Escherichia coli strain that cannot survive in the absence of the unnatural amino acid 3-iodo-L-tyrosine. This synthetic auxotrophy was achieved by conditional production of the antidote protein against the highly toxic enzyme colicin E3. An amber stop codon was inserted in the antidote gene. The translation of the antidote mRNA was controlled by a translational switch using amber-specific 3-iodo-L-tyrosine incorporation. The antidote is synthesized only when 3-iodo-L-tyrosine is present in the culture medium. The viability of this strain rapidly decreased with less than a 1 h half-life after removal of 3-iodo-L-tyrosine, suggesting that the decay of the antidote causes the host killing by activated colicin E3 in the absence of this unnatural amino acid. This containment system can be constructed by only plasmid introduction without genome editing, suggesting that this system may be applicable to other microbes carrying toxin-antidote systems similar to that of colicin E3.