The lambda (λ) T4
rII
exclusion (Rex) phenotype is defined as the inability of T4
rII
to propagate in
Escherichia coli
lysogenized by bacteriophage λ. The Rex system requires the presence of two ...lambda immunity genes,
rexA
and
rexB,
to exclude T4 (
rIIA-rIIB
) from plating on a lawn of
E. coli
λ lysogens. The onset of the Rex phenotype by T4
rII
infection imparts a harsh cellular environment that prevents T4
rII
superinfection while killing the majority of the cell population. Since the discovery of this powerful exclusion system in 1955 by Seymour Benzer, few mechanistic models have been proposed to explain the process of Rex activation and the physiological manifestations associated with Rex onset. For the first time, key host proteins have recently been linked to Rex, including σ
E
, σ
S
, TolA, and other membrane proteins. Together with the known Rex system components, the RII proteins of bacteriophage T4 and the Rex proteins from bacteriophage λ, we are closer than ever to solving the mystery that has eluded investigators for over six decades. Here, we review the fundamental Rex components in light of this new knowledge.
The novel betacoronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread across the globe at an unprecedented rate since its first emergence in Wuhan City, China in ...December 2019. Scientific communities around the world have been rigorously working to develop a potent vaccine to combat COVID-19 (coronavirus disease 2019), employing conventional and novel vaccine strategies. Gene-based vaccine platforms based on viral vectors, DNA, and RNA, have shown promising results encompassing both humoral and cell-mediated immune responses in previous studies, supporting their implementation for COVID-19 vaccine development. In fact, the U.S. Food and Drug Administration (FDA) recently authorized the emergency use of two RNA-based COVID-19 vaccines. We review current gene-based vaccine candidates proceeding through clinical trials, including their antigenic targets, delivery vehicles, and route of administration. Important features of previous gene-based vaccine developments against other infectious diseases are discussed in guiding the design and development of effective vaccines against COVID-19 and future derivatives.
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The T4r
exclusion (Rex) phenotype is the inability of T4
mutant bacteriophage to propagate in hosts (
) lysogenized by bacteriophage lambda (λ). The Rex phenotype, triggered by T4
infection of a
λ ...lysogen, results in rapid membrane depolarization imposing a harsh cellular environment that resembles stationary phase. Rex "activation" has been proposed as an altruistic cell death system to protect the λ prophage and its host from T4r
superinfection. Although well studied for over 60 years, the mechanism behind Rex still remains unclear. We have identified key nonessential genes involved in this enigmatic exclusion system by examining T4r
infection across a collection of
single-gene knockouts. We further developed a system for rapid, one-step isolation of host mutations that could attenuate/abrogate the Rex phenotype. For the first time, we identified host mutations that influence Rex activity and
host sensitivity to T4
infection. Among others, notable genes include
,
,
,
,
,
,
,
, and
They are critical players in cellular osmotic balance and are part of the stationary phase and/or membrane distress regulons. Based on these findings, we propose a new model that connects Rex to the σ
, σ
regulons and key membrane proteins.
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